autonomic (vegetative) nervous system · autonomic (vegetative) nervous system prof. dr. szabolcs...
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Autonomic (vegetative) nervous system
Prof. Dr. Szabolcs Kéri
University of Szeged, Faculty of Medicine, Department of Physiology
2018
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VEGETATIVE or AUTONOMIC NERVOUS SYSTEM (ANS)
Visceral motor innervation of smooth muscle, cardiac muscle, and glands.
functions:→ homeostasis: constancy of internal environment→ allostasis: change of the internal environment (e.g., adaptation to challenges)
parts:→ sympathetic (energy mobilization)→ parasympathetic (energy conservation)→ enteral (gastrointestinal system motor coordination)
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Brainstem nucleiSpinal cord
ANS at glance:
Preganglionic axon
Autonomic ganglion
Postganglionic axon
Visceral effector
organ
Cortex (prefrontal region)
Limbic system(emotions)
Hypothalamus(integrative
role)
Reticularformation
(vital function)
Spinal cord(autonomic
reflexes)
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PARASYMPATHETIC 1:Cranial division
Ganglions
PARASYMPATHETIC 2:Sacral division
SYMPATHETIC: Thoracolumbar division
Motor endplate:nerve ending at skeletal muscleNOT A PART of ANS
ANS: visceromotor/secretion system: smooth/cardiac muscle, glands Skeletomotor system: skeletal muscle
A – epinephrine, NA – norepinephrine, Ach – acetylcholine, N – nicotinic acetylcholine receptor; M – muscarinic acetylcholine receptor; alpha-beta: adrenergic receptor subtypes; MVV – adrenal medulla
Preganglionic fibers
Postganglionic fibers
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Sympathetic nervous system
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1. Preganglionic neuron: thoracic – upper lumbar spinal cord, lateral horn
- Preganglionic axons: B fibers (moderately myelinated, 3 μm, 3-15 m/s)
- White ramus (ramus communicans albicans): preganglionic axon → ventral root → paravertebral ganglion (T1-L2)
2. Ganglionic neuron: para-/prevertebral ganglia (ggl. celiacum/mesentericum)
- Postganglionic axons: C fibers (non-myelinated, 0.5-1.5 μm, 0.25-1.5 m/s)
- Gray ramus (ramus communicans griseus): postganglionic axons run to peripheral nerves
Structure of the sympathetic nervous system
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Visceral afferents
Ggl. spinale
Peripheral nerve
White ramus
Gray ramus
Paravertebralganglion
Prevertebralganglion
Postganglionic fiber
Preganglionic fiber
Postganglionic fiber
Lat.horn
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Neurotransmitters: NOREPINEPHRINE, EPINEPHRINE (co-transmitter: neuropeptid Y, somatostatin)
Release:
- postganglionic terminals (norepinephrine - transmitter)
- adrenal medulla (mainly epinephrine – hormone)
Elimination:
- presynaptic reuptake – monoamine-transporter (Na+-symport)
- metabolism: 1. mitochondria MAO (Monoamine Oxidase)
A – norepinephrine, epinephrine, serotonin
B – dopamine
2. cortex: COMT (Catechol-O-Methyl-Transferase)
endproduct: 3-methoxy-4-hydroxy-phenil-ethylglikol/mandelic acid
Transmitters of the sympathetic nervous system
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Tyrosine
Tyrosinehydroxylase
Dihydro-phenyl-alanine (DOPA)
Dopamine-beta-hydroxylase
DOPA-decarboxylase
Norepinephrine
N -methyltransferase
Epinephrine
Dopamine
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Adrenergic receptors:
α1 (IP3/DAG): postsynaptic (e.g. peripheral vasoconstriction)α2 (cAMP↓): pre-/postsynaptic (presynaptic autoreceptor, negative feedback)
ß1 (cAMP↑): equal affinity to epinephrine and norepinephrine, mainly excitatory (e.g. positive cardiac effects) ß2 (cAMP↑): higher affinity to epinephrine, mainly inhibitory (e.g. peripheral vasodilatation)ß3 (cAMP↑): adiposus tissue, striated muscle (thermogenesis)
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Cardiovascular:
- Heart: positive chrono-, dromo-, inotropic effect (ß1)
- Blood vessels:a. mild activation:
norepinephrine – vasoconstriction (α1) = epinephrine – vasodilatation (ß2) → no changes in total peripheral resistance and blood pressure
b. increased activation:vasoconstriction > vasodilatation →↑total peripheral resistance and blood pressure
Cannon’s alarm reaction (stress reaction)
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Other effects:- Behavioral and psychological (anxiety, fight or flight) (α1, ß2)
- Motor activity of the gastrointestinal tract↓ (α2)
- Bronchial dilatation (ß2)
- Dilated pupils (α1)
- Piloerection (α1)
Metabolic – energy mobilization:- Glycogenolysis, gluconeogenesis↑ (α1, ß2)
- Pancreas ß-cell insulin secretion↓ (α2)
- Lipolysis↑(ß3)
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The adrenal medulla
Adrenalin
Medulla
Epinephrine (80%),norepinephrine
Capillary
Chromaffin cells(pheochromocytes)
Preganglionicfibers
Part of the sympathetic nervous system: modified ganglion + endocrine gland
Chromaffin cells: • Pericapillary cells in medulla,
paraganglionic region• Receiving cholinergic preganglionic
fibers• Synthesis, storage, and release of
epinephrine (co-transmitter: neuropeptid Y)
- Epinephrine to target cells via blood circulation (hormone), degraded by tissue COMT/MAO-A- Alarm reaction (Cannon): physical work, stress, pain, drop in blood pressure, hypoglycemia
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Non-conventional transmission in the ANS
I. Sympathetic cholinergic innervation: sympathetic postganglionic fibers innervating sweat glands and their vessels use acetylcholine as a transmitter
II. Non-adrenergic-non-cholinergic transmission: synaptic activity in ANS independent of acetylcholine and catecholamines • Independent neurotransmitter: Neuropeptid Y, VIP (Vasoactive Intestinal
Polypeptide), ATP• VIP + acetylcholine: exocrine glands (↑ secretion/blood flow)• VIP + NO: relaxation of smooth muscle (e.g. circular smooth muscle in the
gastrointestinal tract)
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Parasympathetic nervous system
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Preganglionic neurons:
A. Autonomic nuclei of the brainstem
→ Edinger-Westphal (III)
→ n. salivatorius superior (VII/V), inferior (IX)
→ n. dorsalis nervi vagi (X) (secretomotor)
→ n. ambiguus (X) (visceromotor)
B. Sacral region
→ Sacral autonomic nucleus
Edinger-Westphal
Salivatorynuclei
Dorsal motor nucleus of vagus
Nucleusambiguus
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Ganglionic neurons:
I. „Head” ganglia:
1. ggl. ciliare (Edinger-Westphal) →m. sphincter pupillae, m. ciliaris
2. ggl. pterygopalatinum (n. salivatorius superior) → glandula lacrimalis, nasalis mucosa
3. ggl. submandibulare (n. salivatorius superior) → glandulasubmandibularis/sublingualis
4. ggl. oticum (n. salivatorius inferior) → glandula parotidea
II. Ganglia in chest, abdomen, pelvis, proximity/wall of target organs (n. dorsalis nervi vagi, n. ambiguus)
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Transmitter: ACETYLCHOLINE (Ach) (co-transmitter: enkephalin, substance P)
Receptor:
- ganglionic neuron: nicotinic (+M1)
- target organ: muscarinic (M) – inhibited by: atropine
M1 (IP3/DAG): gastric acid↑, exocrine glands↑, brain (memory, attention, M4-5), ganglia
M2 (cAMP↓, K+ channel): heart (negative chrono- és dromotropic effect)
M3 (IP3/DAG, NO↑): smooth muscle (direct effect: contraction, NO-effect: relaxation), glands
Neurotransmission in the parasympathetic nervous system
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The synapse between preganglionic fibers and ganglionic neurons
Preganglionic neuron
Nicotinic
M1Peptide
Ganglionicneuron
Early EPSP Late EPSP Peptidergic EPSP/IPSP
VIP, GRP
VIP – Vasoactive Intestinal PolypeptideGRP – Gastrin Releasing Peptide
Postsynaptic action potential
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Vegetative meshwork: • A network of Schwann-cells in which the terminals
of postganglionic fibers are embedded• A single fibber innervates thousands of target cells
(en passant synapse)
Varicosities: • Bulbous enlargements of postganglionic fibers
(„strings of beads”) with vesicles and mitochondria• Inter-varicosities: thin regions linking varicosities
with cytoskeleton• The transmitter is released from the varicosities
and diffuses to target cells
Synapses of the postganglionic fibers
Vesicle:acetylcholine
Receptor
ReceptorSmooth muscle
Contraction
M1/M3
Varicosities
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Autonomic innervation of exocrine glands
Phosphorylation of structural and regulatory proteins
ACH
VIP
Enzymes and mucin secretion in the ducts
Fusion of granules with the apicalmembrane
Parasympathetic:acetylcholine (ACH) and VIP
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Choline reuptakeTransporter (2)
1. Acetylcholinesterase: degradation of acetylcholine into acetate and choline in the synaptic cleft (inhibited by toxic organophosphates)2. Choline reuptake (Na+-symport)3. Acetyl-CoA + choline in presynaptic terminal (choline-acetyltransferase)4. Vesicular acetylcholine transporter (H+-antiport)
Other parasympathetic transmitters:VIP – vasodilatation, glandular secretionNO – smooth muscle relaxationATP – smooth muscle contractionGRP – peptidergic EPSP in gangliaEnkephalin – peptidergic IPSP
Vesicular transzporter (4)
Cholinergic synapse
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Definition: Physiological consequence of spontaneous, low-frequency, baseline activity of vegetative fibers
(1) Skin and vessels of skeletal muscle: sympathetic tone- acute spinal shock → blood pressure drop
(2) Heart: parasympathetic tone
• tone is decreased during inspiration → heart rate↑
• denervation: heart rate↑
(3) Gastrointestinal: parasympathetic tone
• tone is decreased during starvation, chronic stress, and in elderly → constipation
Vegetative tone