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Cardio-Block2
Cardio nerves
| Question | Answer |
|---|---|
| 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 |
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THerzogA
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