NS3 Sympathetic Nervous System PDF

NS3. SYMPATHETIC NERVOUS SYSTEM Physiology IIB Andrea Yool [email protected] Objectives 1. Divisions of the autonomic nervous system and general functions. 2. Origins of the preganglionic and postganglionic fibers. 3. Neurotransm...

NS3. SYMPATHETIC NERVOUS SYSTEM Physiology IIB Andrea Yool [email protected] Objectives 1. Divisions of the autonomic nervous system and general functions. 2. Origins of the preganglionic and postganglionic fibers. 3. Neurotransmitter receptors, their locations and signaling mechanisms. 4. The effects of sympathetic discharge on the target organs. Recommended: Central (CNS) know this diagram Peripheral (PNS) Ascending Descending afferent efferent sensory visceral somatic autonomic RECEPTORS sympathetic parasympathetic MUSCLE enteric EFFERENT Somatic (voluntary) assumed knowledge Autonomic (involuntary)  Overview of functions The autonomic division of the PNS is the equivalent of a “motor system” for viscera, smooth muscles and exocrine glands. Three major divisions are: 1. Sympathetic - participates in the response of the body to stress 2. Parasympathetic - functions in conserving energy and maintaining homeostasis 3. Enteric system- controls smooth muscle in the gut. The autonomic system Most body organs are controlled simultaneously by the opposing parasympathetic and sympathetic systems, but in a given organ, typically one division will dominate. Visceral sensory fibers provide feedback information for reflex controls (subconscious) to regulate blood pressure, heart rate, respiration, and visceral activities.  Origins of autonomic neurons neural plate By week 3 of gestation: development neural groove of brain and spinal cord. 5wks Neural crest cells neural crest form at the neural tube dorsal side, and give rise to newborn the PNS cranial and spinal nerves. Origins of autonomic neurons Neural crest stem cells are born on the dorsal side of the neural tube (1). During development, they detach and migrate to the Developmental Biology periphery (2). Developmental fate is regulated by environmental cues controlling gene expression patterns.  Neural crest cells create the autonomic (parasympathetic, sympathetic and enteric) nervous systems, glia, sensory and pigment cells. A broad array of cell types result from neural crest cell migration. Diagram of spinal afferent and efferent pathways  A simple structural plan--- Unlike the voluntary somatic nervous system (with a single motor neuron connecting the spinal cord to the target tissue), the autonomic nervous system is built as sets of "two-neuron chains.” The first neuron in each set is the preganglionic neuron with its cell body located in the CNS. The second neuron in chain is the postganglionic neuron (originating from neural crest). Adrenaline is released from the adrenal gland into the bloodstream (comparable to a preganglionic structure). Postganglionic neurons are the second links in the two neuron chains Postganglionic neuron cell bodies are clustered together in ganglia, and express nACh receptors similar to those found in skeletal muscle endplate. Sympathetic ganglia are located near the spinal cord. Parasympathetic ganglia are near the target tissue. Sympathetic nervous system organisation The preganglionic cell bodies are located in the thoracic and lumbar spinal cord. The postganglionic cell bodies are clustered into ganglia that are lined up outside the spinal cord (paravertebral ganglia). Sympathetic neurons show a high level of divergence in synaptic connections, enabling rapid widespread activation. Sympathetic nervous system organisation The adrenal glands are in a position equivalent to paravertebral ganglia. adrenal Chemicals medulla released into the adrenaline bloodstream are noradenaline hormones  The “first links” in all three systems are excitatory. The transmitter ACh acts at nicotinic ACh receptors. SOMATIC ACh nAChR ACh SYMPATHETIC PARASYMPATHETIC ACh SPINAL CORD TARGET ORGAN The transmitter action on the target is either excitatory or inhibitory, depending on GPCR coupling. SYMPATHETIC noradrenaline AR: adrenergic receptor (a or b) (+) (-) OR PARASYMPATHETIC (-) (+) ACh mAChR: muscarinic acetylcholine receptor The excitatory or inhibitory effects determined by GPCR coupling give dual control of function. **Important concept** For a given target organ, if AR: adrenergic the effect of the sympathetic receptor (a or b) system is excitatory, then the effect of the parasympathetic will (+) (-) OR typically be inhibitory. (-) (+) The converse is also true. mAChR: muscarinic acetylcholine receptor This allows precise control of organ functions. Maintained influence of the sympathetic system Tonic (sustained) activity balances the opposing actions of the parasympathetic system. Without the sympathetic system, animals could not tolerate any challenging conditions. The balance shifts to maintain homeostasis in an ever changing world. Transporters take up precursor (tyr), and clear the synapse of transmitter (NA) after signaling adrenergic receptors Na-tyrosine cotransporter SPINAL PARAVERTEBRAL TARGET CORD GANGLION TISSUE ACh nAChR Na choline cotransporter noradrenaline (NA) Na-noradrenaline cotransporter Alpha 1 adrenergic receptor phosphatidylinositol Phospholipase C a1 AR DAG bg a GTP IP3 Ca stores Increased cytoplasmic Ca2+, Smooth muscle contraction Beta 1 adrenergic receptor Increased Ca channel activity Adenylate cyclase b1 AR bg a P GTP ATP cAMP PKA Increased cytoplasmic Ca2+, Protein kinase A enhanced muscle contraction Inhibitory responses Alpha 2 receptor (a2): Decreases insulin release, using Kir activation by G-proteins to cause hyperpolarisation (and relaxation). Beta 2 receptor (b2): Increases Ca2+ export from the cell, resulting in smooth muscle relaxation.  Fight or flight response Responses of organs are coordinately regulated to allow a rapid response to a threatening condition. –Heart rate accelerates; –Blood pressure rises; –Blood flow shifts from skin and gut to heart and muscles; –Blood glucose levels rise; –Airways in the lung dilate; –Pupils of the eye dilate. Adrenergic receptor actions Heart sinoatrial node ß1 accelerates rate contractility ß1 increases strength Vascular smooth muscle skin, splanchnic vess a excitation skel muscle vessels ß2 inhibition Bronchiolar smooth musc ß2 inhibition  Smooth muscle controls the resistance pathways excitation --> contraction --> decrease flow inhibition --> relaxation --> increase flow SUMMARY OF KEY DETAILS Heart sinoatrial node ß1 accelerates rate contractility ß1 increases strength Vascular smooth muscle skin, splanchnic vess a contracts (less blood) skel muscle vessels ß2 relaxes (more blood) Bronchiolar smooth musc ß2 relaxes (open airways) GI tract walls a(1), ß2 relaxes sphincters a1 contracts Metabolic funct, liver a, ß2 glucose production, glycogen breakdown (FYI- Both sympathetic and parasympathetic increase salivary gland secretion)  Stress Decreasing psychological stress (and thereby sympathetic activity) can increase resistance to infectious diseases and decrease the risk of heart disease. "He who laughs last didn't get it." -- Helen Giangregorio "He who laughs, lasts." -- Mary Pettibone Poole Adrenergic receptor agents Drugs that are selective for adrenergic receptor subtypes offer therapeutic opportunities: b-1 receptor in the heart “Beta blockers” (antagonists) can be used in the management of cardiovascular disorders. b-2 receptor in the airways Activators (agonists) can be used as bronchodilators in respiratory disorders.  Revision: short answer 1. The autonomic NS divisions (excluding enteric): and. The structural theme is parallel arrays of chains. 2. Preganglionic neurons are located in the spinal cord and use as the transmitter. 3. Sympathetic postganglionic neurons are located in the paravertebral ganglia, and innervate the target organs using as the transmitter. Adrenaline is released from the into the bloodstream. Revision: short answer 4. Using G-protein coupled receptors in the target tissues allows responses to the same transmitter to be or. Excitatory: The intracellular messenger IP3 releases calcium from intracellular stores; or The messenger acts via PKA to upregulate voltage-gated and increase Ca levels. Inhibitory: Activation of (decreases excitability); Activation of Ca transporters results in levels in cytoplasm.  Revision: short answer 5. Relevant subtypes of acetylcholinergic and adrenergic receptors are: nAChR-- excitatory a1 AR-- a2 AR-- b1 AR-- b2 AR-- 6. Overall, the sympathetic system uses adrenergic signaling to create a coordinated systemic “ ” response.