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Cardio-Block2

Cardio nerves

QuestionAnswer
Steps of Neurotransmission Synthesis, Storage in vesicles, release (exocytosis, preceded by Ca2+ influx and an action potential), receptor interation, termination of action (metabolism), or reuptake. *each site represents a potential site for pharmacological intervention.
Major neurotransmitters at the nerve terminals in the autonomic nervous systems ACH and NE
Acetylcholine cholinergic nerves of the Parasymp NS (except glands which are sympathetic NS but use this NT as their NT)
Norepinephrine (noradrenaline) used by adrenergic nerves of the sympathetic nervous system
Epinephrine (adrenaline) hormone released by the adrenal medulla
Difference btw NE and EPI EPI has CH3 instead of H on –NHCH2.
Cotransmission Neuropeptides releasing w/ NE or ACh
Neuropeptides that are released w/ NE or ACH NANC (non-adrenergic, non-cholinergic)
NE can be released with ATP, and/or neuropeptide Y (NPY)
Ach can be released with vasoactive peptide (VIP) and/or substance P (SP), or nitric oxide (NO)
Steps of ACh synthesis: What happens first? Ch uptaken into nerve terminal by a Na+ dependent transmitter
Steps of ACh synthesis: What happens after uptake of Ch? Ch reacts with acetyl CoA (enzyme: choline acetyltransferase [ChAT]) to produce ACh (and CoenzymeA)
Steps of ACh synthesis: What happens after ACh is produced? ACh transported into storage vesicles
Steps of ACh release: What happens first after ACh is in storage vesicles? AP proceeds from neuron cell body to axon terminal where it triggers Ca2+ influx through Ca2+ ion channel.
Steps of ACh release: What happens after Ca2+ influx into axon terminus? multiple ACh vesicles fuse to membrane, release into synaptic cleft by exocytosis
Steps of ACh release: What happens after ACh exocytosis? ACh binds reversibly to postsynaptic receptors
Steps of ACh release: What happens to regulate exocytosis of more ACh? ACh binds to its own presynaptic inhibitory receptor (m2 autoreceptor) as a feedback mechanism to reduce the extent of ACh relese.
Steps of ACh metabolism: What happens to decr ACh in synaptic cleft? ACh metabolized by acetylcholinesterase (AChE, at postsynaptic membrane) to choline and acetic acid
Steps of ACh metabolism: What happens after ACh is broken down? A significant fraction of the choline is reuptaken into the presynaptic nerve terminal for ACh synthesis.
2 classes of cholinergic receptors Nicotinic and muscarinic
Nicotinic Receptor is what type of receptor? ligand gated ion channel
Muscarinic Receptor is what type of receptor? G-protein coupled receptor
What are the 2 subtypes of nicotinic receptors? nn-neuronal and nm-neuromuscular junction
What are the 5 subtypes of muscarinic receptors? m1-m5
ACh action at muscarinic receptors activation of signal transduction process and generation of 2nd messengers that act on downstream cellular pathways
ACh action at nicotinic receptors intiation of a conformational change in the receptor that allows cations, primarily Na+, to enter the neuron and initiate neuronal depolarization
ACh is the NT for: all preganglionic neurons, postganglionic parasympathetic neurons, and sweat glands
Nn-neuronal nicotinic receptors are located on: all post-ganglionic neuron cell bodies, cells of the adrenal medulla
Nm-neuromuscular junction nicotinic receptors are located on: skeletal muscle cells (somatic nervous system)
Muscarinic receptors are located on: all structures innervated by postganglionic parasympathetic nerves, on blood vessels, and on sweat glands (note: sweat glands are innervated by sympathetic, but release ACh from their postganglionic neurons)
**What are the precursors for ACh synthesis and the synthetic enzyme used in that reaction? Choline and Acetyl CoA; Chline acetyltransferase (ChAT) catalyzes ACh synthesis
**Where does ACh synthesis occur in the nerve terminal? In the cytoplasm of cholinergic nerve terminals
**Where does ACh storage take place? in synaptic vesicles
**Upon release of ACh from the nerve terminal, how is it removed from the synapse? metabolized by acetylcholinesterase in the synapse to choline and acetate
**How is the choline generated form ACh metabolism recycled? Approx 60% of the choline generated following ACh metabolism is reuptaken by the Na+ dependent choline carriers located on the presynaptic terminal.
**What are 2 main receptor classes of cholinergic receptors? Nicotinic and muscarinic
Catchol any cmpd that contains a 3,4-dihydroxyphenyl functional group (where R is the remainder of the molecule.
Catecholamine any compound that contains dihydroxyphenyl and amine functional groups. (Ex. Dopamine (DA), NE, and EPI)
Phenylethylamine the alkyl carbons adjacent to the amine are labeled as alpha and beta.
Adrenergic nerve: Synthesis Pathway of NE: Step 1 Tyrosine (Tyr) is converted to Dihydroxyphenylalanine (L-DOPA) by tyrosine hydroxylase (TH) [a hydroxyl group is added to the phenyl ring]
Adrenergic nerve: Synthesis Pathway of NE: Step 2 L_DOPA is converted to dopamine (DA) by aromatic amino decarboxylase (AAAD) [the carboxylate group is removed to yield an amine, occurs in the cytoplasm of the nerve terminal]
Adrenergic nerve: Synthesis Pathway of NE: Step 3 DA is converted to norepinephrine (NE) by dopamine beta hydroxylase (DbetaH) within synaptic vesicles [a hydroxyl group is added to the beta carbon]
Adrenergic nerve: Synthesis and storage of NE: DA synthesized in the cytoplasm and transported into vesicles by vesicular monoamine transporter (VMAT)
DA transport is passive or energy dependent? indirectly energy dependent (ATPase generates H+ w/in the vesicle which is then exchanged for DA by VMAT.
Where does NE synthesis from DA occur? in the vesicles.
Adrenergic nerve: Release of NE in noradrenergic nerve ending: Step 1 An AP proceeds from the neuron cell body to its terminal where it triggers the influx of Ca2+
Adrenergic nerve: Release of NE in noradrenergic nerve ending: Step 2 Ca2+ initiates fusion of some of the vesicles to the mebrane and exocytosis of the NE into the synaptic cleft.
Adrenergic nerve: Release of NE in noradrenergic nerve ending: Step 3 NE binds reversibly to postsynaptic receptors
Adrenergic nerve: Release of NE in noradrenergic nerve ending: Step 4 NE binds to its own presynaptic receptor (a2 autoreceptor) which acts as a negative feedback mechanism to regulate the extent of NE release.
Adrenergic nerve: Reuptake of NE: Step 1: majority of NE through presynaptic transporter (the NE reuptake transporter – NET)
Adrenergic nerve: Reuptake of NE: Step 2: NE can be reutilized for release again via vesicles OR metabolized by monoamine oxidase (MAO) to aldehyde, ammonia, and H2O2 which are then further metabolized.
NE action on receptors: signal tranduction process involving 2nd messengers
What are the two classes of adrenergic receptors? alpha and beta
Beta 3 receptors have higher affinity for EPI or NE? EPI
Beta 2 receptors are acted on by NE or EPI or both? EPI only
**What is the initial precursor for norepinephrine synthesis? Tyrosine
**Where does dopamine synthesis occur in the nerve terminal? in the cytoplasm of the nerve terminal
**Where does NE synthesis occur in the nerve terminal? synaptic vesicles
**Upon release of the NE from the nerve terminal, how is it removed from the synapse? most is reuptaken into the presynaptic nerve terminal and is either reuptaken into vesicles or metabolized by MAO
**What are the two main classes of adrenergic receptors? Alpha and beta
Where does the synthesis of EPI happen w/in the adrenal medulla? chromaffin cells
What is the difference btw EPI and NE synthesis? one addtl enzyme step occurs in NE synthesis to make EPI (amine is methylated by phenylethanolamine N-methyltransferase (PNMT).
Where does the addtl step from NE to EPI occur? in the cytosol then transported into vesicles for release (same process of release as NE)
How does DA synthesis, release, and uptake differ fron NE? no conversion to NE in vesicle, reuptake done by presynaptic dopamine reuptake transporters (DAT, D2 autoreceptor)
How many DA receptor subtypes are there and what are they? 5 total, two classes: excitatory (D1/D5) and inhibitory (D2/D3/D4) effects on AdCy via G-protein coupled mechanisms
Autonomic plexus the intermingling at strategic locations of parasymp and symp fibers coursing to similar locations
What type of parasymp fibers are in autonomic plexii? most are parasymp pregang fibers b/c most parasym ganglia are at the target organ.
What type of symp fibers are in autonomic plexii? most are symp postgang fibers, but certain plexii also contain symp pregang fibers
What are the autonomic plexuses? Cardiac-pulmonary, Aortic, and Pelvic Plexuses
The cardiac-pulmonary plexus is located where? around the aortic arch
The cardiac-pulmonary plexus consists of what type of autonomic fibers? postgang symp fibers from the symp chain and parasymp pregangl fibers from vagus nerve CN X
What are the 2 sympathetic nerves that course to the cardiac-pulmonary plexus? Cervical cardiac and Thoracic cardiac nerves
**Describe the pathway from the cervical cardiac nerves to the cardiac-pulmonary plexus. Symp pregang cell bodies in lateral horn from T1-2→ventral root→spinal nerve→white ramus to symp chain→cervical ganglia to synapse w/NT-ACh, receptor-Nicotinic→postgang fibers leave chain through BACK DOOR→collect to form the cervical cardiac nerve
**Describe the pathway from the thoracic cardiac nerves to the cardiac-pulmonary plexus. Symp pregang cell bodies in lateral horn from T1-4→ventral root→spinal nerve→white ramus to symp chain to synapse near entrance w/NT-ACh, receptor-Nicotinic→symp postgang fibers leave chain through BACK DOOR → collect to form the thoracic cardiac nerve
What nerve fibers course w/cervical and thoracic cardiac nerves? Visceral sensory fibers (receptors of these fibers are located w/in heart wall and sense pain thru nociception and course back to T1-4 spinal nerve level w/sympathetic fibers)
**Describe the path of visceral sensory fibers from the heart wall to the CNS. Course w/symp fibers and follow either the cervical or thoracic cardiac nerves back to the sympathetic chain → white ramus → spinal nerve → dorsal root (ganglia in dorsal root ganglion)→ dorsal horn
What nerve do all the parasympathetic fibers that contribute to the cardiac-pulmonary plexus come from? Vagus Nerve CN X
**Describe the path of the vagus nerve (CN X) to the cardiac nerve? Transverses skull base through jugular foramen, branches off to strs in the neck, in the lower neck it gives off a branch called the cardiac nerve.
The cardiac-pulmonary plexus is broken into: Cardiac and Pulmonary plexuses
Cardiac plexus contains: Symp postganglionic fibers and associated visceral sensory fibers, and Parasymp preganglionic fibers.
**From the surface of the ascending aorta, the cardiac plexus fibers separate into 2 branches: RBB, LBB (course in the adventitia of the right and left coronary artery respectively).
**Sympathetic postganglionic fibers course to the following targets in the heart wall: SA node, AV node, Atrial cardiac muscle fibers, ventricular cardiac muscle fibers
**Adrenergic stimulation leads to: Incr HR, conduction velocity, and ventricular contraction force.
**Parasympathetic preganglionic fibers (vagus nerve fibers) synapse in the parasymp ganglia w/in the epicardium, and then course to the following targets in the heart wall: SA node, AV node, ventricular cardiac muscle fibers
Cholinergic stimulation leads to: Decr HR and conduction velocity
Rate Chronotropy
Contractility Inotropy
Conduction velocity Dromotropy
**During resting, what system predominates, Symp or Parasymp? Vagal/Parasymp rate:60-100bpm
**Cardiac fn is modulated by _________ and __________ in the brain. hypothalamus and the medulla in the lower brainstem
**Cardiac baroreceptors are: visceral sensory stretch receptors that detect changes in the blood pressure
What are the 2 groups of cardiac baroreceptors? Carotid sinus and Aortic arch baroreceptors
Where are the carotid sinus baroreceptors located? Wall of the internal carotid artery
**The carotid sinus baroreceptor fibers course with the ______________________ nerve (containing the visceral sensory fibers) back to the brainstem. Glossopharyngeal (CN IX)
Where are the aortic arch baroreceptors located? wall of the aortic arch
**The aortic arch baroreceptor fibers course with the _____________ back to the brainstem. Vagus nerve(CN X)
______ are responsible for the major resistance to blood flow in the circulatory system. (type of vessel) Arterioles
Normally arterioles are maintained in a state called: vascular tone (partial constriction)
**The extent of vascular tone on arterioles is determined by the interaxn btw ____________ and the _____________. intrinsic factors (myogenic tone), autonomic nervous system
**Symp postgang innervation to smooth muscles uses ____ as the NT that acts mostly at ___ receptors and some ___ receptors in the walls of arterioles to elicit ___________. NE, alpha1, alpha2, vasoconstriction
In veins, the smooth muscle in the tunica media is innervated by symp postgang fibers by NT ____ on __ receptors. NE, alpha1
Bulb-like extensions along the length of terminal axonal processes. Varicosities
The reasons activity of sympathetic neurons varies from region to region in the body: 1. Density of alpha-adrenergic innervation of vessels varies from organ to organ. 2. Sensitivity to NE varies partially due to #1.
Parasymp postgang fibers regulate vascular tone via ACh, VIP, and NO resulting in vasodilation only in: Coronary vessels, Erectile tissue in external genitalia
Adrenal medulla releases 80% ______ and 20% _______ into the systemic circulation, these NTs bnd to their receptors throughout the body. EPI, NE
Created by: THerzogA