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Integrative Physiology Ch. 6 - Communication, Integration, and Homeostasis

How many cells compose the human body? ~75 trillion
Two basic types of physiological signals Electrical and chemical
Electrical signals Changes in a cell’s membrane potential
Chemical signals Molecules secreted by cells into the ECF
_____ signals are responsible for most communication within the body Chemical
Target cells Targets for short, are the cells that receive the electrical or chemical signals
Four basic methods of cell-to-cell communication: (1) gap junctions, (2) contact-dependent signals, (3) local communication, and (4) long-distance communication
Four basic methods of cell-to-cell communication: gap junctions Protein channels that create cytoplasmic bridges between adjacent cells. They allow direct cytoplasmic transfer of electrical and chemical signals between adjacent cells
Four basic methods of cell-to-cell communication: contact-dependent signals They occur when surface molecules on one cell membrane bind to surface molecules on another cell membrane
Four basic methods of cell-to-cell communication: local communication Communication by chemicals that diffuse through the ECF
Four basic methods of cell-to-cell communication: long-distance communication Occurs through a combination of electrical signals carried by nerve cells and chemical signals transported in the blood.
Connexins A gap junction forms from the union of membrane-spanning proteins called connexins, on two adjacent cells
Connexon The united connexins create a protein channel called a connexon that can open or close.
Syncytium When the connexon is open the connected cells function like a single cell that contains multiple nuclei (syncytium)
What kind of molecules flow through connexons when they’re open? Ions and small molecules such as amino acids, ATP, and cyclic AMP diffuse directly through from one cytoplasm to the other. Larger molecules cannot pass through
The only means by which electrical signals can pass directly from cell to cell Gap junctions
Are all gap junctions the same? No, there are over 20 different isoforms of connexins that may mix and match, leading to a variety of different degrees of selectivity of the resultant connexons
Where does contact-dependent signaling commonly occur? In the immune system and during growth and development, such as when nerve cells send out long extensions that must grow from the central axis of the body to the distal ends of the limbs
CAMs “Cell adhesion molecules”. They act as receptors in cell-to-cell signaling. CAMs are linked to the cytoskeleton and to intracellular enzymes. CAMs transfer signals in both directions across cell membranes
Local communication is accomplished by _____ and _____ signaling Paracrine and autocrine
Paracrine signal A chemical that acts on cells in the immediate vicinity of the cell that secreted the signal.
Autocrine signal If a chemical acts on the cell that secreted it, it’s an autocrine signal (acts on itself)
Paracrine and autocrine signals reach their target cells by… …diffusing through the interstitial fluid. Distance is a limiting factor for diffusion so the effective range of paracrine signals is restricted to adjacent cells
Example of paracrine signaling Histamine is a paracrine molecule that is released from damaged cells. It diffuses into nearby capillaries making them more permeable to white blood cells and antibodies in the plasma. They also cause fluid to accumulate and swell
Which cells in the body can release paracrine signals? All of them
Most long-distance communication between cells is the responsibility of… …the nervous and endocrine systems
The endocrine system communicates by using… …hormones
Hormones Chemical signals that are secreted into the blood and distributed all over the body by the circulation. While hormones will contact many cells, only those with receptors for the hormones are target cells
How does the nervous system communicate? It uses a combination of chemical and electrical signals to communicate over long distances. An electrical signal travels along a neuron until it reaches the end of the cell where it’s translated into a chemical signal.
What are the electrical-turned-chemical signals released from neurons called? Neurocrines
Neurotransmitter A neurocrine molecule that diffuses from the neuron across a narrow extracellular space to a target cell and has a rapid effect
Neuromodulator If a neurocrine acts more slowly (than a neurotransmitter), that is, it functions as an autocrine or paracrine molecule, then it is a neuromodulator
Neurohormone If a neuron releases a neurocrine that diffuses into the blood for distribution it is a neurohormone
The similarities between the neurohormones from the nervous system and classic hormones from the endocrine system cause… …their distinctions to be blurred so that the two systems are a continuum rather than two different entities
Cytokines A large and diverse family of regulators produced throughout the body. They are small cell-signaling proteins and can be proteins, peptides, or glycoproteins.
What do cytokines control? Cell development, cell differentiation, and the immune response
How do cytokines differ from hormones? Cytokines act on a broader spectrum of target cells. Also they’re not produced by specialized cells the way hormones are (all nucleated cells can produce cytokines in response to stimuli), and they are made on demand
If not made on demand like cytokines, how are most hormones prepared? They’re made in advance and stored in the endocrine cell until needed
Receptor proteins Proteins to which signal molecules (paracrine, autocrine, or hormones) bind
Rule about receptors A cell cannot respond to a chemical signal if the cell lacks the appropriate receptor proteins for that signal
Ligand The signal molecule that binds to a receptor
The ligand is known as the _____ because… First messenger because it brings information to its target cell
How is the receptor activated? The ligand-receptor binding activates the receptor
What does the receptor do after being activated? It in turn activates one or more intracellular signal molecules
What do the activated intracellular signal molecules do? The last signal molecule in the pathway initiates synthesis of target proteins or modifies existing target proteins to create a response
The general pattern of a signal pathway Signal molecules –(binds to)-> Receptor protein –(activates)-> Intracellular signal molecules –(alters)-> Target proteins –(create)-> Response
Chemical signals fall into two broad categories based on their lipid solubility: Lipophilic and lipophobic
Where can target-cell receptors be found? In the nucleus, cytosol, or cell membrane as integral proteins
Lipophilic signal molecules They diffuse through the phospholipid bilayer of the cell membrane and bind to cytosolic receptors or nuclear receptors wherein they often modify gene expression. This process is slow (1 hour+). Most of these are hormones
Lipophobic signal molecules Unable to diffuse through membrane, instead they remain in the EFC and bind to receptor proteins on the cell membrane. A very rapid response time, within milliseconds to minutes.
Four categories of membrane receptors Receptor-channels, receptor-enzymes, G protein-coupled receptors, integrin receptors
Signal transduction The process whereby an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a response
First and second messengers The extracellular signal molecule (ligand) is the first messenger; the intracellular molecules form a *second messenger system*
Transducer A device that converts a signal from one form into a different form; e.g. the transducer in a radio converts radio waves into sound waves. In biology, transducers convert the message of ECF ligands into ICF responses
Signal amplification In cells, signal amplification turns one signal molecule into multiple second messenger molecules. This begins when the ligand combines with its receptor and the ligand-receptor complex turns on an amplifier enzyme
Amplifier enzyme An enzyme that activates several more molecules
Signal transduction pathway pattern: (1) Ligand binds to and activates a protein or glycoprotein membrane receptor.
Signal transduction pathway pattern: (2) The activated receptor turns on its associated proteins which may be protein kinases (which transfer phosphates from ATP to proteins) or amplifier enzymes (which create ICF second messengers)
Signal transduction pathway pattern: (3) Second messengers alter the gating of channels (opening or closing them, affecting the cell’s membrane potential) then increase intracellular calcium which will bind to proteins and change their function, creating cellular response
Signal transduction pathway pattern: (4) Second messengers will also change enzyme activity, especially protein kinases or protein phosphatases
Signal transduction pathway pattern: (5) The proteins modified by the calcium bonding or phosphorylation (or dephosphorylation) control one or more of the following: metabolic enzymes, motor proteins, gene expression, and membrane transport/receptors
Signaling cascade A signaling cascade starts when a stimulus (ligand) converts inactive molecule A (receptor) to an active form. Active A then converts inactive B to active B, which converts inactive C to active C and so on.
The most common amplifier enzymes Adenylyl cyclase, guanylyl cyclase, and phospholipase C
Commons second messengers Ca^2+, cAMP, cGMP, IP_3, DAG
Receptor enzymes Have two regions: receptor region on the ECF side, and enzyme region on ICF side. Enzyme region may be on a different protein than the receptor. The enzyme will be either a protein kinase (e.g. tyrosine kinase) or guanylyl cyclase
Function of guanylyl cyclase Converts GTP to cGMP. Found in membrane cytosol. Activated by receptor-enzyme nitric oxide (NO)
Ligands for receptor-enzymes include… …the hormone insulin as well as many growth factors and cytokines. Note: the insulin receptor protein has intrinsic tyrosine kinase activity. Most cytokines don’t have intrinsic enzyme activity and instead activate cytosolic enzymes
What kinds of enzymes are activated by cytokine receptor proteins A cytosolic enzyme called Janus family tyrosine kinase, abbreviated JAK kinase
G protein-coupled receptors Large membrane-spanning proteins that cross the bilayer 7 times. The cytoplasmic tail is linked to the G protein
G proteins A 3-part membrane transducer molecule. When inactive they’re bound to guanosine diphosphate (GDP). Exchanging GDP for GTP activates the G protein.
What do G proteins do when activated (1) open an ion channel in the membrane, or (2) alter enzyme activity on the cytoplasmic side of the membrane
G proteins linked to _____ make up the bulk of all known signal transduction mechanisms Amplifier enzymes
Two most common amplifier enzymes for G protein-coupled receptors Adenylyl cyclase and phospholipase C
The types of ligands that bind to the G protein-coupled receptors The types of ligands that bind to the G protein-coupled receptors include hormones, growth factors, olfactory molecules, visual pigments, and neurotransmitters
Function of adenylyl cyclase Converts ATP to cAMP. Found in membrane. Activated by G protein-coupled receptor.
Function of phospholipase C Converts membrane phospholipids to IP3 and DAG. Found in membrane. Activated by G protein-coupled receptor
The G protein-coupled adenylyl cyclase-cAMP system: (1) Signal molecule binds to G protein-coupled receptor, which activates the G protein.
The G protein-coupled adenylyl cyclase-cAMP system: (2) G protein turns on adenylyl cyclase, an amplifier enzyme
The G protein-coupled adenylyl cyclase-cAMP system: (3) Adenylyl cyclase converts ATP to cAMP
The G protein-coupled adenylyl cyclase-cAMP system: (4) cAMP activates protein kinase A
The G protein-coupled adenylyl cyclase-cAMP system: (5) Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response
The G protein-coupled phospholipase C system summary When a signal molecule activates this G protein-coupled pathway, phospholipase C (PL-C) converts a membrane phospholipid into two second messengers: diacylglycerol (DAG) and inositol triphosphate (IP_3)
Diacylglycerol (DAG) A nonpolar diglyceride that remains in the membrane and interacts with protein kinase C (PK-C), a Ca^2+-activated enzyme on the cytoplasmic face of the cell membrane. PK-C phosphorylates cytosolic proteins for signal cascade
Inositol triphosphate (IP_3) A water-soluble messenger molecule that leaves the membrane and enters the cytoplasm. It then binds to a calcium channel on the ER, opening up the channel, allowing Ca^2+ to diffuse into the cytosol. Ca^2+ = signal molecule
The G protein-coupled phospholipase C system: (1) Signal molecule activates receptor and associated G protein
The G protein-coupled phospholipase C system: (2) G protein activates PL-C, an amplifier enzyme
The G protein-coupled phospholipase C system: (3) PL-C converts membrane phospholipids into DAG which remains in the membrane, and IP_3 which diffuses into the cytoplasm
The G protein-coupled phospholipase C system: (4) DAG activates PK-C which phosphorylates proteins
The G protein-coupled phospholipase C system: (5) IP_3 opens Ca^2+ channel on ER, releasing Ca^2+ into the cell creating a Ca^2+ signal
Integrin receptors: ECF Membrane-spanning integrins have receptors on the ECF side binding either to proteins of the matrix or to ligands such as antibodies or blood clotting molecules.
Integrin receptors: ICF In the ICF, integrins bind to cytoskeleton via anchor proteins. If a ligand binds to a receptor on the ECF, integrins will activate intracellular enzymes or alter the organization of the cytoskeleton
What important role do integrin receptors play? Blood clotting is defective in individuals who lack integrin receptors on their platelets
The simplest receptors are… (also, where are they found?) …ligand-gated ion channels (receptor-channels) and most of them are neurotransmitter receptors found in the nerve and muscle. They’re also the most rapid.
How do receptor-channels work? When a ligand binds to the receptor-channel protein, a channel gate opens or closes, altering the cell’s permeability to an ion. The membrane potential is rapidly effected, creating an electrical signal
Acetylcholine-gated cation channel of the skeletal muscle The neurotransmitter acetylcholine released by a neuron binds to the acetylcholine receptor and opens the channel, allowing Na+ to flow in, depolarizing the cell. A cascade results which leads to contraction of the muscle
How does calcium enter the cytosol Through voltage-gated Ca^2+ ion channels or through ligand-gated or mechanically gated channels. It can also enter from within organelles if it is released by second messengers such as IP_3
Where are most calcium ions stored, and how does it get there? In the ER, where it is concentrated by active transport
Effects of calcium ions entering the cytoplasm: (1) They bind to the protein *calmodulin*, found in all cells, which then alters enzyme or transporter activity or the gating of ion channels. I.e. calmodulin alters proteins after binding to Ca^2+
Effects of calcium ions entering the cytoplasm: (2) They bind to regulatory proteins and alter movement of contractile or cytoskeletal proteins e.g. microtubules. E.g. Ca^2+ binding to the regulatory protein troponin initiates muscle contraction in a skeletal muscle cell
Effects of calcium ions entering the cytoplasm: (3) They bind to regulatory proteins to trigger exocytosis of secretory vesicles.
Effects of calcium ions entering the cytoplasm: (4) They bind directly to ion channels to alter their gating state.
Effects of calcium ions entering the cytoplasm: (5) Entry into a fertilized egg initiates development of the embryo
Gases as signal molecules Soluble gases are short-acting paracrine/autocrine signal molecules that act close to where they’re produced
The best known gaseous signal molecules Nitric oxide (NO) is best known; there’s also: carbon monoxide and hydrogen sulfide
Half-life The time required for a signal (or any substance) to lose half of its activity
NO as a signal In endothelial tissues NO is produced by nitric oxide synthase (NOS): arginine + O2 –(NOS)-> NO + citrulline. The NO diffuses into target cells where, through a cascade, ultimately relaxes blood vessels.
NO in the brain Acts as a neurotransmitter and neuromodulator
Carbon monoxide (CO) as a signal Activates the same pathway as NO: guanylyl cyclase which in turn activates cGMP and ultimately acts as a blood vessel reactant. It can also be a neurotransmitter like NO.
Hydrogen sulfide (H2S) as a signal Acts in the cardiovascular system to relax blood vessels. Garlic is a major source of sulfur-containing precursors which explains why eating garlic may be protective to the heart
Orphan receptors Receptors with no known ligand
Eicosanoids Lipid-derived paracrine signals. They are all derived from arachidonic acid, a 20-carbon fatty acid. They ultimately act on their target’s G protein-coupled receptors
The synthesis process network that produces arachidonic acid is known as the… …arachidonic acid cascade
Arachidonic acid cascade Phospholipase A2 (PLA2)--guided by hormones/other signals--acts on membrane phospholipids to create arachidonic acid. The acid will then either act as a second messenger itself or be converted into eicosandoid paracrines
The two major eicosanoid paracrines (derived from arachidonic acid). Also, what happens to them after they’re produced? Leukotrienes and prostanoids. These lipid-soluble molecules can diffuse out of the cell and combine with G protein coupled-receptors on neighboring cells to exert their action
Leukotrienes Created by lipoxygenase acting on arachidonic acid. Leukotrienes are produced by certain types of white blood cells. They play a role in asthma and anaphylaxis
Prostanoids Produced when the enzyme cyclooxygenase (COX) acts on arachidonic acid. Prostanoids include prostaglandins and thromboxanes which signal a huge assortment of actions, e.g. prostaglandins play a role in inflammation
Brief description of how NSAIDs (e.g. aspirin/ibuprofen) work They inhibit COX enzymes and decrease prostaglandin synthesis. Prostaglandins play a role in inflammation and inflammation causes pain due to a release of chemicals that stimulate nerve endings
Another example (other than eicosanoids) of lipid signal molecules Sphingolipids, which are extracellular signals that regulate inflammation, cell adhesion/migration, and cell growth/death. Like eicosanoids they combine with G protein-coupled receptors in their target’s membranes
For most signal molecules, the target cell response is determined by… …the receptor (or its associated intracellular pathways), not the ligand. That is, the same ligand can have two different effects on two different tissues
Different molecules with similar structure may be able to bind to… …the same receptor’s binding site. This can result in competition
Example of specificity and competition with binding site receptors Both neurocrines norepinephrine and epinephrine bind to both alpha and beta adrenergic receptors. However, alpha adrenergic receptors have higher affinity for norepinephrine and beta receptors prefer epinephrine
When a ligand binds with a receptor, one of two events follows: Either the ligand activates the receptor and elicits a response, or the ligand occupies the binding site and prevents the receptor from responding.
Agonists Ligands that activate receptors
Antagonists Ligands that prevent (block) receptors from responding
Note: what does “endogenous” mean? Produced by the body
Example of a pharmacologically synthesized agonist The modified estrogens in birth control pills are agonists of naturally occurring estrogens but have been chemically modified to protect them from breakdown and extend their active life
The effect of epinephrine binding to the two isoforms: alpha vs. beta-2 adrenergic receptors When epinephrine binds to the alpha receptor, e.g. in the intestinal tract blood vessels, the blood vessels constrict. When epinephrine binds to the beta-2 receptor, e.g. in skeletal muscle blood vessels, blood vessels dilate
What happens when a signal molecule is present in the body in abnormally high concentrations for a sustained period of time? Initially an enhanced response is created, but then the target cells may attempt to bring their response back to normal by either down-regulation or desensitization of the receptors for the signal
Down-regulation A decrease in receptor number. The cell can physically remove receptors from the membrane through endocytosis
Desensitization A faster method of decreasing cell response than down-regulation. It is achieved by binding a chemical modulator to the receptor protein. E.g. phosphorylating beta receptors
Desensitization diminishes the target cell’s response regardless of… …the concentration of the signal molecule
Drug tolerance A condition in which the response to a given dose decreases despite continuous exposure to the drug; it occurs due to down-regulation and desensitization
Up-regulation The insertion of more receptors into the membrane. E.g. if a neuron is damaged and can’t release normal amounts of neurotransmitter, the target cell may up-regulate its receptors
How does a cell terminate a response from a Ca^2+ signal? By pumping the calcium back into the ER or into the ECF
How can receptor activity be stopped? One way is by degrading the ligands with enzymes in the ECF. Another is by transporting the messengers into neighboring cells
Once a ligand binds to a receptor, how can activity be terminated? By endocytosis of the receptor-ligand complex. Once in the cytoplasm the ligands are removed and the receptors return to the membrane via exocytosis
Disease caused by toxin: Bordetella pertussis Whooping cough: the toxin blocks inhibition of adenylate cyclase (i.e., keeps it active)
Homeostasis is a continuous process that uses a _____ to monitor key functions, which are often called _____ Physiological control system; regulated variables
In its simplest form, any control system has three basic parts: (1) an input signal, (2) a controller to respond to input signals, and (3) an output signal
The input signal of the physiological control system The regulated variable and a specialized sensor. If the variable moves out of its desirable range, the sensor is activated and sends a signal to the controller
Physiological control system’s controller The integrating center (often neurons or endocrine cells) – it evaluates information coming from the sensor and initiates a response that is designed to bring the regulated variable back into the desired range
Physiological control system’s output The effector: muscles or other tissues controlled by the integrating center
Cannon’s postulates describing regulated variables and control systems (1) the nervous system preserves the “fitness” of the internal environment; (2) some systems of the body are under tonic control; (3) some systems of the body are under antagonistic control, (4) one signal can have varied effects
Cannon’s postulates describing regulated variables and control systems: (1) Fitness = compatible with normal function. Nervous system regulates blood volume, pressure, osmolarity, body temp., etc.
Cannon’s postulates describing regulated variables and control systems: (2) There are agents in the body such as blood vessel constriction that are constantly moderated by increasing or decreasing input (rather than turning on or off)
Cannon’s postulates describing regulated variables and control systems: (3) There are agents in the body that are constantly moderated sending opposing signals to them, e.g. parasympathetic and sympathetic pathways
Cannon’s postulates describing regulated variables and control systems: (4) As we already learned, one signal can have different effects on different receptors
Local control A relatively isolated change occurs in the vicinity of a cell or tissue and evokes a paracrine or autocrine response
Reflex control pathways Respond to changes that are widespread throughout the body, i.e. *systemic*. This is a long-distance pathway
Systems involved in long-distance reflex control pathways The nervous and endocrine systems. Cytokines are also involved
A reflex pathway can be broken down into two parts: A response loop and a feedback loop
Three components of the reflex loop and their steps. I.e. Steps of a reflex Input signal (stimulus/sensor -> afferent pathway), integration of the signal (integrating signal), and output signal (efferent pathway -> effector -> response).
Stimulus/sensor -> afferent pathway Stimulus = disturbance or change that sets the pathway in motion. Sensor = receptor that picks up the stimulus. When altered, the sensory receptor will send a signal, AKA afferent pathway, linking the receptor to an integrating center
Integrating center Evaluates the incoming signal, compares it with the *setpoint* (desired value) and decides on an appropriate response.
Efferent pathway -> effector -> response The output signal, or efferent pathway, is initiated by the integrating center. This is the electrical or chemical signal that’s sent to the effector (AKA target). The effector carries out the appropriate response to normalize the situation
Sensory receptors vs. receptor molecules Sensory receptors refer to specialized cells, parts of cells, or complex multicellular receptors such as the eye/ear/nose/skin/etc. This is a different application of the word receptor. Receptors can refer to both
Central receptors Receptors located in, or closely linked to, the brain
Peripheral receptors Receptors residing elsewhere in the body
Threshold All sensory receptors have a threshold, a minimum stimulus that must be achieved to set the reflex response in motion
Do endocrine reflexes that are not associated with the nervous system have sensory receptors? No they’re not associated with the nervous system so they don’t use sensory receptors to initiate their pathways
In endocrine reflexes, what’s the integrating center? The endocrine cell
In neural reflexes, what’s the integrating center? Central nervous system (brain/spinal cord)
Two levels of response for any reflex control pathway Cellular response: takes place in target cell; and systemic response: describes what the events mean to the organism as a whole
Factors that influence an individual’s setpoint for a given variable Inheritance and the environmental conditions in which the organism has become accustomed.
Acclimatization The adaptation of physiological processes to a given set of environmental conditions if it occurs naturally
Acclimation The adaptation of physiological processes to a given set of environmental conditions if it is induced artificially in a laboratory setting
Feedback loop The response “feeds back” to influence the input portion of the pathway
_____ feedback loops are homeostatic; _____ feedback loops are not Negative (keeps system near setpoint); positive
How well an integrating center succeeds in maintaining stability via negative feedback loops depend on…? …the sensitivity of the system. If not very sensitive, the regulated variable will oscillate around the setpoint. Some sensors in physiological systems are more sensitive than others
Positive feedback loop The response reinforces the stimulus rather than decreasing it (like negative feedback loops)
Example of positive feedback loops Hormonal control of uterine contractions during childbirth. The baby drops and puts pressure on cervix. Oxytocin is released causing uterus to contract, putting more pressure on cervix causing oxytocin release
Feedforward control Reflexes that enable the body to predict that a change is about to occur and start the response loop in anticipation of the change
Example of feedforward control Salivation, initiated by the sight, smell, or even thought of food
Circadian rhythm Daily biological rhythm. Humans have many circadian rhythms including blood pressure, body temperature, and metabolic processes. E.g. you feel cold at night due to the circadian rhythm-controlled thermoregulatory reflex
Are cortisol concentrations in the body constant? Now they vary; they’re a circadian rhythm-controlled process
While neural and endocrine reflexes can be relatively simple, _____ can be very complex Neuroendocrine reflexes
Specificity of reflex pathways: neural vs. endocrine Neural control is very specific because each neuron has a target cell. Endocrine control is less specific (hormone exposed to many cells)
Speed of reflex pathways: neural vs. endocrine Neural reflexes are much faster than endocrine pathways, with electrical signals reaching speeds of up to 120 m/sec.
Duration of action of reflex pathways Neural control is of much shorter duration than endocrine control. The neurotransmitter is rapidly removed from the target after the response. Endocrine, while slower to start, lasts much longer and are ongoing
Stimulus intensity of reflex pathways Signal strength of a neuron is constant. Thus to express intensity, the frequency of the signaling through the neuron increases. In the endocrine system, the intensity is reflected by the amount of hormone released
Knee-jerk response A blow to the knee activates a stretch receptor which sends a signal through the afferent neuron to the spinal cord (the integrating center). The spinal cord sends a signal back through an efferent neuron to contract the muscles
4 basic modes of cell-cell communication Gap junctions, contact-dependent signals, local communication, long-distance communication
Type of junctions between contractile cardiac cells Gap junctions, through which ions flow to regulate contraction
Contact-dependent signals Interaction between two membrane-associated molecules on two adjacent cells
Two types of local communication Autocrine and paracrine
How far away between paracrine signaling? What’s the limit (distance) for communication? About 100 microns is the limit
Long distance communication is accomplished by… …the endocrine and nervous systems
Concentration gradient on which hormones travel when secreted The gland that secretes the hormone is filled with them, so secretion into the blood occurs down their concentration gradient.
Nervous communication does not require… …the blood
Neurotransmitter Molecules that are secreted by neurons across a small gap to the target cells neurotransmitters are made in relatively LOW quantities
Do endocrine glands make a relatively large or small amount of material compared to neurons? Large: it’s more of a brute force method of communication than neural communication
Endocrine vs. exocrine Endocrine: secreted from gland rather than through duct. What is secreted is a hormone
How do lipophilic and lipophobic correspond to hydrophobic and hydrophilic? Lipophilic = hydrophobic; lipophobic = hydrophilic (i.e. hydrophilic hormones need to use surface receptors to enter cells)
cAMP is a… …second messenger, activated by adenylyl cyclase, an amplifier enzyme
Explain how the G protein is exactly activated by the coupled receptor. How does that work? Activated receptor bind to G-protein (a trimer) causing it to released GDP. GTP then binds to G protein, altering its conformation and causing it to detach from receptor. The altered G protein now binds with the effector (adenylyl cyclase)
After the G protein binds with the effector (amplifier enzyme), how does it eventually detach? GTP is hydrolyzed to GDP; the G protein then reassociates with the remainder of the dissociated G protein (beta and gamma)
Recap: parts of the G-protein G_beta/gamma: the part that dissociates from the G-protein (along with the receptor) when GTP binds with it. G_alpha: the part that binds with the effector after being dissociated from G_beta/gamma and receptor
G protein may work in a different pathway, not cAMP but… …PL-C -> IP_3
Adrenergic receptors bind to… …epinephrine
Major adrenergic receptors. What type of receptor are they? Alpha-1 (important for vasoconstriction), alpha-2, beta-1 (important for the beating of the heart), beta-2, beta-3. They’re all G protein-coupled receptors
How do adrenergic receptors lead to vasoconstriction (thus increasing blood pressure)? Use an alpha-1-adrenergic receptor an example. Epinephrine binds to G protein-coupled receptor (an alpha-1 adrenergic receptor). PL-C is activated which causes PKC activation. Increases in Ca^2+ leads to muscle contraction -> vasoconstriction
An agonist to an adrenergic receptor would… (Example of an agonist?) …mimic epinephrine. It looks enough like the hormone to be able to bind to the receptor. Example: pseudophed, which constricts blood vessels in the nasal cavity leading to nasal decongestion
Where do alpha-1 adrenergic receptors reside? On smooth muscle cells
Most receptors on the heart are what type of receptor? Beta-1 adrenergic receptors
Catecholamine storm after heart attack The body releases a ton of catecholamines in an attempt to recover from the injury. This is chronic and results in a down-regulation of beta-adrenergic receptors on the heart
GRK G protein-couple receptor kinase
Give detailed explanation of the process of down-regulation GRK phosphorylates the ACTIVATED receptor. A molecule called arrestin then binds to the receptor and escorts it to a clathrin coated vesicle for endocytosis. The “sorting endosome” determines whether or not to recycle it
Sorting endosome – How does it determine whether or not to recycle the G protein-coupled receptor? The decision is whether to degrade the receptor or send it back out to the surface. It depends on how long the agonist (ligand) is there and how high the concentration is. If it’s chronic, the sorting endosome will degrade the receptor
Chronic beta-blocker therapy results in… …up regulation of beta-receptors (because beta-blockers are beta-adrenergic receptor antagonists). It has to be chronic in order for up regulation to occur
Where is blood pressure changes sensed in the body? How does this play a role in homeostasis Carotid artery which senses the bp change and sends a signal to the brain which decides the proper response. The brain will either initiate a reflex response or there can be a local change and a local response.
How to shut off a positive feedback loop? An outside factor is required to shut it off
Why would you want a positive feedback loop E.g. for ovulation, wherein you want a powerful surge of response
Created by: Intellex_



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