ANS Review

ANS maintains you & allows you to respond to the environment SYMPATHETIC Mobilizes body to expend energy Targets widely distributed organ systems Blood vessels, sweat glands, piloerector muscles

FEAR

Sympathetic & adrenal medulla: Fight or flight response mobilizes the body to expend energy for extreme sustained physical exertion . Cardiovascular System Increase in heart rate & force of contraction  increased cardiac output (5L/min  25-40L/min) Increase in BP Redistribution of blood flow Respiratory System Airways are dilated Digestive System GI function (motility and secretions) inhibited Metabolism Glucose is mobilized Lipolysis is stimulated Metabolic rate increases

Stimuli that release adrenal medullary catecholamines Physiological stressors Psychological: emotional states - fear Metabolic Hypothermia Pathological stressors Severe hemorrhage Heart attack Pain NOTE: Asthmatic attacks do not release CAs

ANS maintains you & allows you to respond to the environment SYMPATHETIC Mobilizes body to expend energy Targets widely distributed organ systems PARASYMPATHETIC Restorative role; conserves energy Discrete targeted control

General feature of ANS Tonically active system Always have basal level of end organ activity Often modulates ongoing spontaneously generated activity (heart; GI tract) Activity controlled reflexly & most autonomic reflexes are readily affected by emotional state

Schematic ANS: Organization post pre Parasympathetic Cranial Spinal cord pre T1 post Sympathetic Thoraco-lumbar pre Collateral ganglia Adrenal Splanchnic nerve L3 Parasympathetic post pre Sacral S2 S3 S4 Schematic ANS: Organization

Schematic ANS: Wiring of ganglia 1:1/1:2 pre Targeted control Parasympathetic Cranial Spinal cord Diffuse targets Divergence/convergence T1 Sympathetic pre Collateral ganglia Adrenal Splanchnic nerve L3 Parasympathetic 1:1/1:2 pre Sacral S2 S3 S4 Targeted control Schematic ANS: Wiring of ganglia

Neuroeffector junction: Sympathetic postganglionic nerve terminal is a diffusely distributed complex branching network with varicosities (swellings) Synaptic vesicle

ANS TRANSMITTERS Ach Ach Ach Ach Ach Ach Ach Spinal cord Sympathetic postganglionics to sweat glands Ach Ach T1 Ach Biological inactivation: Breakdown: acetylcholinesterase Resupply: De novo synthesis in terminal Adrenal L3 Ach Ach S2 S3 S4 All preganglionic neurons release Ach All postganglionic parasympathetic neurons release Ach Sympathetic postganglionics  general sweat glands (except sweat gland on palms, soles of feet, & underarms) release Ach

ANS TRANSMITTERS Ach Ach Ach NE Ach NE EPI – 80% Ach Ach Spinal cord Ach T1 NE Ach NE EPI – 80% Biological inactivation of NE: REUPTAKE Resupply of NE: recycling & new synthesis Adrenal L3 Ach Ach S2 S3 S4 Sympathetic postganglionic neurons release NE (except to generalized sweat glands; Adrenal medulla releases NE and EPI (80%) Peptides also in LDCV in terminals along with Ach & NE

Peptides Stored in LDCV Never located at plasma membrane Released only by high frequency stimulation Peptides augment actions of low molecular weight transmitter (ACh or NE) Biological inactivation: breakdown by peptidases

ANS RECEPTORS – ganglion - nicotinic Ach Ach nicotinic Spinal cord nicotinic Ach T1 NE Ach Differences between ganglionic & skeletal NMJ nicotinic receptors: Subunit composition Sensitivity to antagonists nicotinic L3 Ach Ach S2 S3 S4 nicotinic Somatic motor nerve Skeletal NMJ All postganglionic neurons, cells of the adrenal medulla & skeletal NMJ have nicotinic cholinergic receptors

ANS RECEPTORS (+) (-) (+) Ach Ach Spinal cord muscarinic Sweat gl. (+) Sympathetic postganglionics to generalized sweat glands release Ach (+) Ach T1 Ach muscarinic L3 Ach Ach (+) S2 S3 S4 Cholinergic receptors of the muscarinic type are on effector tissues innervated by parasympathetic postganglionic neurons and on generalized sweat glands

Schematic ANS ANS RECEPTORS -Adrenergic NE EPI NE Alpha-1 & 2 post pre Parasympathetic Cranial Spinal cord NE pre T1 post Sympathetic pre EPI NE Alpha-1 & 2 Beta-1 & 2 Adrenal Splanchnic nerve L3 Parasympathetic post pre Sacral S2 S3 S4 Schematic ANS

Receptors for NE Alpha-1 receptors Excitatory  contraction of smooth muscle Most important location -- smooth muscle of blood vessels Insensitive - require high concentrations of agonist; NE & EPI ~ equipotent Under physiological conditions, a-1 receptors are activated by NE released from sympathetic nerves. EPI released from adrenal in response to stress never reaches high enough concentrations in the circulation to activate a-1 receptors Effects mediated by IP3 production

Receptors for NE Alpha-2 receptors are presynaptic Inhibitory receptors located on nerve terminals. Autoreceptors on sympathetic postganglionic terminals; Hetero-receptors on terminals of parasympathetic nerves of the GI tract bind NE, released from adjacent postganglionic sympathetic nerves. Activation of a-2 receptor reduces evoked transmitter release by reducing Ca2+ entry into presynaptic terminal a-2 heteroreceptors mediate sympathetic inhibition of GI tract

BETA-1 RECEPTORS Excitatory response to both NE & EPI Location – heart: beats faster and more strongly Beta-1 receptor is very sensitive to both NE & EPI – so heart can be stimulated by NE released from sympathetic nerves or EPI released from the adrenal medulla Beta-1 effects mediated by stimulation of cAMP production

BETA-2 RECEPTORS inhibitory  relaxation of smooth muscle very sensitive to EPI, but not NE activated in response to stress (when adrenal medulla secretes EPI into the circulation) found on smooth muscle of airways, GI tract, & blood vessels supplying skeletal muscle (along with alpha-1 receptors) Beta-2 agonists used for acute treatment of asthmatic attacks stimulate production of cAMP

Blood vessels of skeletal muscle

Transmitter Receptor Action Target Signalling Mechanism ACh nicotinic +++ Postganglionic neurons Ligand gated ion channel depolarization muscarinic --- Smooth m Glands Heart GPCR IP3 induced Ca release Opens K+ channel NE a-1 a-2 ---- Nerve varicosities IP3 induced Ca release Ca entry EPI b-1 cAMP b-2

Examples of ANS Reflexes Pupillary light reflex Stress activation of the adrenal medulla Reflex regulation of the GI tract (CNS & LOCAL) Parasympathetic Nervous System Vago-vagal activation of stomach (CNS) Gastro-colic reflex (CNS) Enteric Nervous System - Locally mediated stereotyped movements (e.g. peristalsis) Sympathetic Nervous System Global inhibition (stress response - CNS) Enterogastric reflex: selective local inhibition: Tonic inhibition (local)

ENS PARASYMPATHETIC SYMPATHETIC