Neurotransmission: Autonomic & Somatic Motor Nervous Systems PDF

NEUROTRANSMISSION: The Autonomic & Somatic Motor Nervous Systems Geraldine Jaca-Corporal, MD, DPBA  Neurotransmission process by which signaling molecules called neurotransmitters are released by a neuron (the presynaptic neuron), and bind to and activate the recepto...

NEUROTRANSMISSION: The Autonomic & Somatic Motor Nervous Systems Geraldine Jaca-Corporal, MD, DPBA  Neurotransmission process by which signaling molecules called neurotransmitters are released by a neuron (the presynaptic neuron), and bind to and activate the receptors of another neuron (the postsynaptic neuron).  Autonomic Nervous System Visceral, Vegetative or Involuntary Nervous 1 System 2 Regulates autonomic function without conscious control 3 Supply all the structures in the body except skeletal muscles 4 Contain peripheral ganglia  Autonomic Nervous System Distal synapses are outside the cerebrospinal 1 axis 2 May form extensive peripheral plexuses 3 Postganglionic nerves are nonmyelinated 4 When interrupted, smooth muscles & glands retain some level of spontaneous activity  Somatic Nerves Supply the skeletal muscle No peripheral ganglia Synapses are located within the cerebrospinal axis Do not form peripheral plexuses Motor nerves to skeletal muscles are myelinated. Visceral Afferent Fibers - conduct sensory impulses (usually pain or reflex sensations) from the viscera, glands, and blood vessels to the central nervous system. Efferent Fibers - are conducting cells that carry information from the central nervous system (the brain and spinal cord) to muscles and organs throughout the body.  Visceral Afferent Fibers Spinal Cranial Nerve (Parasympathetic) (Sympathetic) carries mechanoreceptor & carries sensations of temperature chemosensory information & tissue injury of mechanical, or thermal origin enters the CNS via: ascend by spinothalamic & CN V (trigeminal) - face & head spinoreticular tracts, dorsal column CN VII (facial) - tongue CN IX (glossopharyngeal) - hard palate, upper oropharynx CN X (vagus) - lower part of oropharynx, larynx, trachea, esophagus, thoracic abdominal organs  Peripheral Autonomic System (Efferent) - 2 divisions: 1) Sympathetic or Thoracolumbar Outflow 2) Parasympathetic or Craniosacral Outflow Acetylcholine (ACh): all preganglionic fibers, most postganglionic parasympathetic nerves, few postganglionic sympathetic nerves - “cholinergic” Nitric Oxide (NO): some postganglionic parasympathetic nerves “nitrergic” Norepinephrine (NE, noradrenaline, levarterenol): most of the postganglionic sympathetic nerves “adrenergic”  Sympathetic Nervous System extends from T1 to L2 or L3 segment 1 3 locations: PARAVERTEBRAL, PREVERTEBRAL, TERMINAL PARAVERTEBRAL GANGLIA: 2 white rami - carry preganglionic myelinated fibres gray rami - carry postganglionic fibres PREVERTEBRAL GANGLIA: 3 consists of celiac, superior mesenteric, aorticorenal & inferior mesenteric ganglia  Sympathetic Nervous System TERMINAL GANGLIA: 1 - consist of ganglia of urinary bladder & rectum and cervical ganglia - lie near the organs they innervate 2 Adrenal medulla: embryologically and anatomically similar to SNS - derived from neural crest 3 Adrenal medulla: epinephrine Sympathetic Fibers: norepinephrine  Paraympathetic Nervous System CN 3 CN 7 CN 9 CN 10  Paraympathetic Nervous System S2-S4: form the pelvic nerves (nervi erigentes) : synapse in terminal ganglia within the bladder, rectum & sexual organs  Enteric Nervous System - sensorimotor control organised into 2 nerve plexuses: 1) Myenteric (Auerbach’s) plexus: contraction & relaxation of GI smooth muscle 2) Submucosal (Meissner’s) plexus: secretory & absorptive functions of GI epithelium  Sympathetic Parasympathetic Somatic System System System *terminal ganglia *terminal ganglia *innervate skeletal far from the near or within the muscle directly effector cells organ innervated without ganglionic *ratio: 1:20 or *ratio: 1:1 relay more *ratio in myenteric *preganglionic plexus: 1:8000 *neurotransmitter: fiber: ACh *preganglionic fiber: ACh acting on *postganglionic ACh nicotinic receptor fiber: NE acting on *postganglionic receptors fiber: ACh acting on muscarinic receptors * Sympathetic & Parasympathetic Neurotransmitters are antagonists. * However, their activities on specific structures may be independent or integrated. Effect on heart & iris: show functional antagonism Effect on male sexual organs are complementary & integrated to promote sexual function.  Neurotransmission 1 Hypothesis: Each neuron contains only one transmitter substance. 2 However, synaptic transmission in many instances may be mediated by the release of more than one neurotransmitter. Enkephalin, substance P, neuropeptide Y, VIP, 3 somatostatin, ATP, adenosine, Nitric Oxide are found in nerve endings - can depolarize or hyperpolarize postsynaptic cells.  Steps in Neurotransmission passage of an impulse along an axon Conduction or muscle fiber. Transmission passage of an impulse across a synaptic or neuroeffector junction.  Axonal Conduction Resting potential: -70mV 1 * Intracellular ion: K+ * Extracellular ion: Na+ Action potential 2 1st phase: influx of Na+ - positive overshoot 2nd phase: inactivation of Na+ channel & delayed opening of K+ 3 Adjacent axons are activated & excitation of adjacent portion of axonal membrane occurs.  Axonal Conduction 4 This results to propagation of action potential without decrement along the axon. 5 Myelinated fibres: occurs in nodes of Ranvier - jumping or saltatory conduction * Tetrodotoxin (puffer fish) & Saxitoxin (shellfish): block Na+ channel - preventing influx of Na+ — block axonal conduction Batrachotoxin (steroidal alkaloid from South American frog): increase permeability of Na+ channel — persistent depolarization — PARALYSIS. Scorpion toxins: cause persistent depolarization by inhibiting the inactivation process.  Junctional Transmission Action potential at axon terminals initiates transmission of an excitatory or inhibitory impulse across the synapse or neuroeffector junction.  Junctional Transmission Storage and release of neurotransmitter caused 1 by action potential Promotes fusion of axoplasmic Exocytosis of Influx of Calcium membrane and neurotransmitter vesicles  Junctional Transmission Combination of neurotransmitter w/ post junctional 2 receptors & production of the post junctional potential. 1) Increase permeability to Na2+ & occasionally Ca2+ — depolarization — excitatory postsynaptic potential (EPSP) 2) Increase in Cl- — hyperpolarization — inhibitory postsynaptic potential (IPSP) 3) Increase permeability to K+ which is directed out of the cell — hyperpolarization — IPSP  Junctional Transmission 3 Initiation of postjunctional activity. EPSP IPSP * propagates action * opposes excitatory potential potentials * smooth muscle: Ca2+ release; enhance muscle tone * gland cells: Ca2+ mobilization; secretion  Junctional Transmission 4 Destruction or dissipation of the transmitter. *Acetylcholinesterase ACh * Diffusion * Simple diffusion + reuptake by NE Amino acid axonal terminals * Active transport into neutrons & surrounding glia Peptides * Hydrolyzed by peptidases & dissipated by diffusion  Junctional Transmission 5 Non-electrogenic functions. The continual quantal release of neurotransmitters in amounts insufficient to elicit response is important in transjunctional control of neurotransmitter action. Synthesis, Storage & Release of Acetylcholine 2 1 1) Uptake of CHOLINE by Na2+ & Cl— - dependent transport system that can be blocked by HEMICHOLINIUM. 2) CHOLINE + ACETYL moiety of Acetyl 3 CoA = ACETYLCHOLINE (ACh) catalyzed by choline acetyl transferase (ChAT) 3) ACh transported into storage vesicles by a carrier that can be inhibited by VESAMICOL. 4) ACh stored with potential cotransmitters (Co-T) (ATP, VIP) at neuroeffector junctions. Synthesis, Storage & Release of Acetylcholine 5) Depolarization allows entry of Ca2+ — promotes fusion of vesicular membrane w/ cell membrane. 6) Involves vesicle-associated membrane proteins (VAMPS) & 6 synaptosome-associated proteins (SNAPS). 5 7) Exocytosis - release of ACh that can 7 be blocked by BOTULINUM TOXIN. 8 8) ACh interact w/ muscarinic & nicotinic receptors — produce characteristic response. Synthesis, Storage & Release of Acetylcholine 9) ACh can also act on presynaptic mAChRs or nAChRs to modify its own release. 11 10) ACETYLCHOLINESTERASE (AChE) 10 terminates action ACh by metabolism to CHOLINE & ACETATE. 11) CHOLINE is recycled after reuptake for ACh synthesis - rate 9 limiting step in ACh synthesis.  Acetylcholine Receptors Nicotinic Muscarinic ligand-gated G-protein couple receptor 5 subunits 5 subtypes - M1-M5 1) Muscle type : skeletal muscle M1, M3, M5 - increase cAMP M2, M4 - decrease cAMP 2) Neuronal type - PNS, CNS  Synthesis of Catecholamines Synthesis, Storage & Release of Norepinephrine 1 1) TYROSINE transported into the varicosity — DOPA by Tyrosine 2 Hydoxylase (TH) — DOPAMINE by Aromatic L-Amino Acid Decarboxylase 4 (AAADC) 3 2) DOPAMINE taken up into vesicles by VMAT2 that can be blocked by Reserpine 3) VMAT2 can also transport cytoplasmic NE 4) DOPAMINE converted to NE within the vesicle by Dopamine-β-hydoxylase (DβH) & stored w/ NPY & ATP  Synthesis, Storage & Release of Norepinephrine 5) Depolarization — increase Ca2+ — fusion of vesicular membrane w/ membrane of the varicosity thru interaction w/ VAMPs & SNAPs 5 6) EXOCYTOSIS - release of NE, NPY, ATP 6 7) NE interact with α & β receptor to produce characteristic response 9 7 8 8) NPY activates NPY receptors (Y1-Y5) & removed from synapse by peptidases 9) ATP activates P2X & P2Y receptors & cleared by nucleotidases. Synthesis, Storage & Release of Norepinephrine 10) NE cleared via: *neuronal uptake transporter (NET) 11 * dilution by diffusion out of the junctional cleft and uptake at extraneuronal sites by ENT, OCT 1 & OCT 2. 10 11) Once transported in the cytosol, NE can be re-stored in the vesicle or metabolized by monoamine oxidase (MAO) Metabolic Disposition of Catecholamines 1) NE & Epinephrine deaminated to 1 1 DOPGAL by monoamine oxidase (MAO) 2 2) DOPGAL to: * 3,4 dihydroxymandelic acid (DOMA) by aldehyde dehydrogenase (AD) 3 * 3,4 dihydroxyphenyl glycol (DOPEG) by aldehyde reductase (AR) 3)DOPEG to 3-methoxy, 4 hydroxyphenyl-glycol (MOPEG) by catechol-0-methyl transferase (COMT) Metabolic Disposition of Catecholamines 4) MOPEG to MOPGAL by alcohol dehydrogenase (ADH) 6 6 5) MOPGAL to VANILLYL MANDELIC ACID (VMA) by aldehyde dehydrogenase (AD) 6) Other route: w/ COMT * NE to Normetanephrine * Epinephrine to Metanephrine 4 MOPGAL 5 VMA  Adrenergic Receptors α β order of potency: order of potency: epinephrine > norepinephrine isoproterenol > epinephrine > >> isoproterenol norepinephrine α1 : α1A , α1B , α1D β1, β2, β3 : activate adenylyl - activated by phenylephrine & cyclase — increases cAMP methoxamine α2 : α2A , α2B , α2C α1 :- αagonist - clonidine - reduce 1A , α1B , α1D sympathetic outflow - decrease in BP  Adrenergic Receptors α β α2A : inhibits NE release β1: myocardium : antinociceptive effects, : epinephrine & NE equipotent sedation, hypothermia, hypotension β2: smooth muscles ; other sites : epinephrine 10-50x more α2B: mediates vasoconstriction potent than NE α2C : modulate dopamine β3: adipose tissue neurotransmission & : norepinephrine 10x more behavioural responses potent than Epinephrine α1: produce prostaglandins & leukotrienes : relaxation of GI smooth muscle GOOD MORNING 😇😇😇