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MK Physio

Basic Cell Membrane & Potentials (PREMATRIC)

Membrane Functions 1. Physical isolation 2. Regulation of exchange with environment 3. Sensitivity 4. Structural support
Membrane Function: Physical isolation Separates intracellular/extracellular contents (proteins, enzymes, ions)
Membrane Function: Regulation of exchange with environment Transporting nutrients in and metabolic wastes out "Compartmentalization with communication"
Membrane Function: Sensitivity Capable of being stimulated by external agents *protein sensors (receptors) transfer information by binding specific signaling molecules (e.g., hormones, NTs)
Membrane Function: Structural support Anchoring points for many of the cytoskeletal fibers
Membrane composition and structure 1. Lipids 2. Proteins 3. Carbohydrates *composition of lipids & proteins varies from cell to cell
Membrane composition and structure: Lipids Made up of phospholipids and steroid lipids (cholesterol); all membrane lipids are AMPHIPATHIC (head is hydophilic, tail is hydrophobic) -hydrophobic interior serves as a barrier
Membrane composition and structure: Proteins Provides membrane with specialized function
Membrane composition and structure: Carbohydrates Important in recognition of cell types: -immunity (outside of the cell) -intercellular signaling - during tissue growth, cells will not trespass past boundaries of other tissues
The fluid quality of the membrane - Not static/solid sheets of molecules locked rigidly - Membrane held together primarily by HYDROPHOBIC ATTRACTIONS (mutual exclusion of water) - When molecules are close together, VAN DER WAALS ATTRACTIONS (+ and -) reinforce hydrophobic interactions
Phospholipids Main lipid constituent of most membranes -similar to triglyceride fats, but have only 2 fatty acid tails rather than 3 -Amphipathic
Phospholipid tail -3rd hydroxy group of glycerol is joined to a phosphate group, which is negative in electrical charge -add'l small molecules (usually charged or polar) can be linked to the phosphate group.
Amphipathic quality of Phospholipids -Hydrophilic molecules (polar head) dissolve in H2O b/c contain charged groups -> interact with H2O -Hydrophobic molecules (hydrocarbon tails) insoluble in H2O b/c all/most of their atoms are uncharged & nonpolar (no energetically favorable interactions)
Phospholipid conformation -One tail usually has 1 or more cis-double bonds (unsaturated) while the other tail does not (saturated) -cis-configuration causes the chain to kink- restricts the conformational freedom of the fatty acid. (structural integrity allows for a bilayer)
Membrane Proteins 30% of proteins encoded in a cell's genome are membrane proteins. for example: -Sarcoplasmic Reticulum of skeletal muscle have only a few different proteins while plasma membranes have > 100 different proteins.
Membrane Protein Orientation All membrane proteins have a specific orientation in the membrane (Na+/K+ ATPase, and Ca2+ ATPase of SR = asymmetrical; ATP hydrolysis occurs on the cytoplasmic face
Membrane Protein Structure Compact 3-D structures are are either 1. Integral: all or part penetrates the phospholipid bilayer 2. Peripheral: do not interact with hydrophobic core of bilayer
Membrane Protein Functions 1. Transport 2. Enzymes 3. Receptor sites 4. Cell Adhesion 5. Attachment to the cytoskeleton
Membrane Protein Functions: Transport Proteins a hydrophilic channel (mostly for ions) or a carrier/pump
Membrane Protein Functions: Enzymes built into the membrane with active sites exposed to aqueous medium
Membrane Protein Functions: Receptor sites binding domain is exposed to ECF; may induce signal transduction through membrane
Membrane Protein Functions: Cell adhesion adjacent membrane proteins may be hooked together to form intercellular junctions
Membrane Protein Functions: attachment to cytoskeleton important in maintaining cell shape and fixing the location of certain membrane proteins
Properties of Membranes (REVIEW) "Impermeable" to polar molecules and ions -Highly flexible & durable -Contain "mix" of lipids (phospholipids & cholesterol) -Contain proteins that have a purpose -In more complex cells, contain carbohydrates -Asymmetric w/ respect to structure & func
Membrane Locations 1. External Membranes (cell membrane) 2. Internal membranes (nucleus, organelles)
Typical forces across a membrane 1. Chemical gradient 2. Electrical gradient 3. Electrochemical gradient
Chemical Gradient the difference in [ ] across membrane (more collisions in a higher [ ] push the molecules to areas of lower [ ])
Electrical gradient the difference in charge between two adjacent areas -outside membrane: net positive charge -inside membrane: net negative charge
Electrochemical gradient combines membrane potential and [ ] gradient which can work additively to increase the driving force
Simple diffusion net flux of molecules from one region to another via random thermal motion
Net rate of diffusion (J) J = C x P x A where: C is Magnitude (steepness) of the [ ] gradient P is Permeability of the membrane to the substance A is surface area of the membrane (higher surface area, easier to diffuse)
Permeability takes into account: 1. Partition coefficient (solubility in lipid (more perm) vs. H2O (less perm) 2. diffusion coefficient (mol wt & viscosity) 3. membrane thickness (ex: when sick, mucous layer on membrane makes thicker, harder to diffuse thru)
Osmotic Flow Water flows across a semipermeable membrane b/c of differences in SOLUTE [ ]. -The [ ] of impermeable solutes establish osmotic PRESSURE differences.
A cell in a hypotonic solution will... Burst
A cell in a hypertonic solution will... Shrivel
A cell in an isotonic solution will... Stay the same
Facilitated diffusion: Channels 1. Channel proteins form hydrophilic pores across membrane (allows small water-soluble ions to pass) 2. Down [ ] gradient (passive) ex: Na+ and K+ channels
2 distinctions between ion channels and aqueous pores 1. Channels are ION SELECTIVE: narrow pores so ions contact walls; only those with appropriate SIZE and CHARGE will pass 2. Gated
Membrane Permeability High Perm: hydrophobic molecules and small uncharged molecules (O2 and CO2) Low Perm: Hydrophilic molecules, Charged molecules (ions), Large molecules (macromolecules)
Hypotonic Solution has a lower osmotic pressure than the contents of the cell
Isotonic Solution has the same osmotic pressure as the contents of the cell
Hypertonic Solution has a higher osmotic pressure than the contents of the cell
Osmolarity the [ ] of impermeable particles in solution -increasing the [ ] of imperm particles decreases the [ ] of water -decreasing the [ ] of particles increases the [ ] of water
How to determine Osmolarity 1. [ ] of solute 2. # of particles the solute dissociates into in solution (ex. CaCl2 = 3 particles)
Osmolarity Equation (mOsm/L) = g x C where g is the # of particles per mole in solution (Osm/mol) and C is the concentration (mmol/L)
Types of Carrier-Mediated Transport 1. Facilitated diffusion 2. Primary Active Transport 3. Secondary Active Transport
Primary Active Transport -Mediated by carrier proteins -moves molecules against [ ] gradient -requires direct input of energy ex: Na+/K+ ATPase Pump
Secondary Active Transport -Mediated by carrier proteins -moves molecules against [ ] gradient -uses energy from [ ] gradient of another molecule obtained thru primary active transport (does not use energy directly) ex: Na+/Glu CoTransporter (Na+ down [ ] grad, Glu up [ ] grad)
Membrane Potential The separation of charges across a membrane (ex: neuron = -70 mV)
What is responsible for Membrane Potential? Difference in ionic [ ] & selective permeability of channels -RMP is maintained by Na+/K+ pump (pumps 3 Na+ ions out/2 K+ ions in per cycle. utilizes 1 ATP per cycle.)
Intracellular [ ] of certain ions Na+ = 15 mM K+ = 150 mM Ca2+ = .0002 mM Cl- = 13
Extracellular [ ] of certain ions Na+ = 150 mM K+ = 5 mM Ca2+ = 2 mM Cl- = 150
Ohm's Law I = mV/R where: I = current mV = voltage R = resistance
Conductance -aka. permeability -The conductance (g) of the membrane to an ion = reciprocal of resistance (ie, 1/R) -conductance of channel depends on probability that channel is open. (K+ has largest resting conductance (most perm b/c @ -70, it's channels are open
Magnitude of potential depends on the degree of separated changes. (the more charges there are on each side, increases the charge separation).
Forces acting on Resting Membrane Potential 1. Unequal transport of cations generates a membrane potential. 2. maintains [ ] gradient. (ion [ ] difference & selective permeability determines the resting membrane potential of -70.
Resting Membrane potential The ion with the largest resting conductance will have the greatest influence on RMP. (in this case, K+ = -90 b/c channels are more open than Na+ channels = +60)
Nerst equation -Determines equilibrium potential for a given ion across a membrane. E = 61 x log { [ ]out / [ ]in } where 61 is a constant that incorporates: the ideal gas constant (R), absolute temperature (T), ion's valance (z), and Faraday's number (F) (E is mV
Nerst equation for K+ Ek = 61 x log { [5mM] / [150mM] } = -90 mV (5mM outside cell; 150mM inside cell)
Membrane Potential (bottom line) -[K+] has largest resting conductance (K+ leak or resting channels, open all the time) and thus the greatest influence on RMP -changes in [K+] in ECF affect the RMP of all cells
Changes in membrane potential as signals (two types) 1. Graded potentials: short distance signals 2. Action potentials: long distance signals (several hundred feet/sec; fast enough to avoid a dog bite)
Components of the Action Potentials 1. threshold 2. Depolarization 3. Repolarization phase 4. Hyperpolarization afterpotential (upward deflection = decrease in potential; downward deflection = increase in potential)
AP Threshold the value of the MP which, if surpassed, leads to the all-or-nothing initiation of an AP.
AP Depolarization the rising phase of the AP (a large # of Na+ channels start to open once threshold is reached. - net movement of Na+ into the cell starts)
AP Repolarization phase the return of the MP to the resting potential (voltage gated Na+ channels start to close and voltage gated K+ channels start to open; net movement of Na+ into cell stops; net movement of K+ into cell starts (delayed rectifying response))
AP Hyperpolarizing afterpotential time at which the MP is actually more negative than the RMP (voltage gated K+ channels remain open for a relatively long time before eventually closing - net movement of K+ into the cell continues for a while before stopping)
Action Potential Features 1. Large, rapid changes 2. Depolarizing only 3. Caused by opening enough Na+ channels to activate positive feedback (threshold) until voltage change is sufficient to close Na+ channels. 4. Repolarization is by opening K+ channels to leave cell
Action Potential Features (cont.) 5. Na/K ATPase readjusts ion distribution 6. all-or-none events; subthreshold stimuli won't induce AP 7. propagated with the same shape/size along entire length of nerve/muscle 8. size & shape of AP's differ from 1 excitable tissue to another
Channels 1. Highly selective pores that open and close (only appropriate size/charge may pass) 2. 10^5 times greater transport from channel than carrier protein (but usually not coupled to energy source (down gradient process) 3. gated, not continuously open
Voltage-gated Channels (opened & closed by changes in membrane potential) 1. channel changes conformation to exist at lowest state of energy (highest stability) 2. lowest state of energy depends on membrane potential b/c different conformations have diff. charge distributions
stages for a channel 1. Rest: Na+ channel is in closed conformation (low energy, high stability) 2. Depolarized: channel is open (exists only transiently) (high E, low S). -inactivated is lower E still, so after a period spent in open position, channel becomes inactivated.
How do AP's convey information? 1. shape & size of AP usually invariant, the FREQUENCY of AP can be used in the code for info transmission. (higher the freq, more important the message.) 2. Max freq is limited by duration of absolute refractory period (1 msec) to ~1000 impulses/sec
Graded Potentials generated at synapses or by an extrinsic stimulus (ex. light)
Graded Potential Features 1. names differ according to location 2. small, local changes 3. may be depolarizing or hyperpolarizing 4. direction and magnitude of response is proportional to direction and mag of stimulus. 5. decay rapidly with distance. (short-lived)
Graded potential names in different locations 1. in muscles: endplate potential 2. in neurons: postsynaptic potential 3. sensory organs: receptor potential
Ligand gated channels opened and closed by the binding of corresponding ligands (ex: on dendrites, there are ligand gated Na+ channels which respond to excitatory NT's and ligand gated Cl- channels which respond to inhibitory NT's)
electrochemical equilibrium the chemical and electrical forces of a particular ion are balanced so that there is no net movement of molecules
Absolute Refractory Period time after the initiation of one action potential when it is impossible to initiate a second action potential (voltage gated Na+ channels are inactivated)
Relative Refractory Period time after one AP is initiated when can have a 2nd AP (due to hyperpolarization), but only with a greater stimulus (depolarization) than necessary to initiate the 1st. -Na+ channels are starting to reset, but inward K current is still greater than at RMP
Created by: Kanarema



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