98761_Ch02_Chapter 02 5/7/10 6:32 PM Page 31 chapter 2 Neurophysiology I. AUTONOMIC NERVOUS SYSTEM (ANS) ■ is a set of pathways to and from the central nervous system (CNS) that innervates and reg- ulates smooth muscle, cardiac muscle, and glands. ■ is distinct from the somatic nervous system, which innervates skeletal muscle. ■ has three divisions: sympathetic, parasympathetic, and enteric (the enteric division is discussed in Chapter 6). A. Organization of the ANS (Table 2-1 and Figure 2-1) 1. Synapses between neurons are made in the autonomic ganglia. a. Parasympathetic ganglia are located in or near the effector organs. b. Sympathetic ganglia are located in the paravertebral chain. 2. Preganglionic neurons have their cell bodies in the CNS and synapse in autonomic ganglia. ■ Preganglionic neurons of the sympathetic nervous system originate in spinal cord segments T1–L3, or the thoracolumbar region. ■ Preganglionic neurons of the parasympathetic nervous system originate in the nuclei of cranial nerves and in spinal cord segments S2–S4, or the craniosacral region. 3. Postganglionic neurons of both divisions have their cell bodies in the autonomic ganglia and synapse on effector organs (e.g., heart, blood vessels, sweat glands). 4. Adrenal medulla is a specialized ganglion of the sympathetic nervous system. ■ Preganglionic fibers synapse directly on chromaffin cells in the adrenal medulla. ■ The chromaffin cells secrete epinephrine (80%) and norepinephrine (20%) into the circulation (see Figure 2-1). ■ Pheochromocytoma is a tumor of the adrenal medulla that secretes excessive amounts of catecholamines and is associated with increased excretion of 3-methoxy- 4-hydroxymandelic acid (VMA). B. Neurotransmitters of the ANS ■ Adrenergic neurons release norepinephrine as the neurotransmitter. ■ Cholinergic neurons, whether in the sympathetic or parasympathetic nervous system, release acetylcholine (ACh) as the neurotransmitter. ■ Nonadrenergic, noncholinergic neurons include some postganglionic parasympathetic neu- rons of the gastrointestinal tract, which release substance P, vasoactive intestinal peptide (VIP), or nitric oxide (NO). 31 98761_Ch02_Chapter 02 5/7/10 6:32 PM Page 32 32 Board Review Series: Physiology table 2-1 Organization of the Autonomic Nervous System Characteristic Sympathetic Parasympathetic Somatic* Origin of preganglionic nerve Nuclei of spinal cord Nuclei of cranial nerves III, segments T1–T12; L1–L3 VII, IX, and X; spinal cord (thoracolumbar) segments S2–S4 (craniosacral) Length of preganglionic Short Long nerve axon Neurotransmitter in ganglion ACh ACh Receptor type in ganglion Nicotinic Nicotinic Length of postganglionic Long Short nerve axon Effector organs Smooth and cardiac Smooth and cardiac Skeletal muscle muscle; glands muscle; glands Neurotransmitter in Norepinephrine (except sweat ACh ACh (synapse is effector organs glands, which use ACh) neuromuscular junction) α α β β Receptor types in effector 1, 2, 1, and 2 Muscarinic Nicotinic organs *Somatic nervous system has been included for comparison. ACh = acetylcholine. CNS Effector organ Postganglionic Preganglionic Parasympathetic ACh ACh Muscarinic Nicotinic receptor receptor (NN) Preganglionic Postganglionic Sympathetic ACh Nicotinic Norepinephrine* α1, α2, β1, β2 receptor (NN) receptors Epinephrine (80%) Adrenal Norepinephrine (20%) ACh Adrenal gland Nicotinic receptor Skeletal Somatic muscle ACh Nicotinic receptor (NM) *Except sweat glands, which use ACh. FIGURE 2-1 Organization of the autonomic nervous system. ACh = acetylcholine; CNS = central nervous system. 98761_Ch02_Chapter 02 5/7/10 6:32 PM Page 33 Chapter 2 Neurophysiology 33 table 2-2 Signaling Pathways and Mechanisms for Autonomic Receptors Receptor Location G Protein Mechanism Adrenergic α ↑ 2+ 1 Smooth muscle Gq IP3/Ca α ↓ 2 Gastrointestinal tract Gi cAMP β ↑ 1 Heart Gs cAMP β ↑ 2 Smooth muscle Gs cAMP Cholinergic + + NM (N1) Skeletal muscle — Opening Na /K channels + + NN (N2) Autonomic ganglia — Opening Na /K channels ↑ 2+ M1 CNS Gq IP3/Ca ↓ M2 Heart Gi cAMP ↑ 2+ M3 Glands, smooth muscle Gq IP3/Ca IP3 = inositol 1,4,5-triphosphate; cAMP = cyclic adenosine monophosphate. C. Receptor types in the ANS (Table 2-2) 1. Adrenergic receptors (adrenoreceptors) a. `1 Receptors ■ are located on vascular smooth muscle of the skin and splanchnic regions, the gas- trointestinal (GI) and bladder sphincters, and the radial muscle of the iris. ■ produce excitation (e.g., contraction or constriction). ■ are equally sensitive to norepinephrine and epinephrine. However, only norepi- nephrine released from adrenergic neurons is present in high enough concentra- α tions to activate 1 receptors. ■ Mechanism of action: Gq protein, stimulation of phospholipase C, and increase in 2+ inositol 1,4,5-triphosphate (IP3) and intracellular [Ca ]. b. `2 Receptors ■ are located on sympathetic postganglionic nerve terminals (autoreceptors), platelets, fat cells, and the walls of the GI tract (heteroreceptors). ■ often produce inhibition (e.g., relaxation or dilation). ■ Mechanism of action: Gi protein inhibition of adenylate cyclase and decrease in cyclic adenosine monophosphate (cAMP). c. a1 Receptors ■ are located in the sinoatrial (SA) node, atrioventricular (AV) node, and ventricular muscle of the heart. ■ produce excitation (e.g., increased heart rate, increased conduction velocity, increased contractility). ■ are sensitive to both norepinephrine and epinephrine, and are more sensitive than α the 1 receptors. ■ Mechanism of action: Gs protein, stimulation of adenylate cyclase and increase in cAMP. d. a2 Receptors ■ are located on vascular smooth muscle of skeletal muscle, bronchial smooth mus- cle, and in the walls of the GI tract and bladder. ■ produce relaxation (e.g., dilation of vascular smooth muscle, dilation of bronchi- oles, relaxation of the bladder wall). ■ are more sensitive to epinephrine than to norepinephrine. ■ α are more sensitive to epinephrine than the 1 receptors. ■ β Mechanism of action: same as for 1 receptors. 98761_Ch02_Chapter 02 5/7/10 6:32 PM Page 34 34 Board Review Series: Physiology 2. Cholinergic receptors (cholinoreceptors) a. Nicotinic receptors ■ are located in the autonomic ganglia (NN) of the sympathetic and parasympathetic nervous systems, at the neuromuscular junction (NM), and in the adrenal medulla (NN). The receptors at these locations are similar, but not identical. ■ are activated by ACh or nicotine. ■ produce excitation. ■ are blocked by ganglionic blockers (e.g., hexamethonium) in the autonomic ganglia, but not at the neuromuscular junction. ■ Mechanism of action: ACh binds to α subunits of the nicotinic ACh receptor. The nicotinic ACh receptors are also ion channels for Na+ and K+. b. Muscarinic receptors ■ are located in the heart (M2), smooth muscle (M3), and glands (M3). ■ are inhibitory in the heart (e.g., decreased heart rate, decreased conduction velocity in AV node). ■ are excitatory in smooth muscle and glands (e.g., increased GI motility, increased secretion). ■ are activated by ACh and muscarine. ■ are blocked by atropine. ■ Mechanism of action: (1) Heart SA node: Gi protein, inhibition of adenylate cyclase, which leads to opening of K+ channels, slowing of the rate of spontaneous Phase 4 depolarization, and decreased heart rate. (2) Smooth muscle and glands: Gq protein, stimulation of phospholipase C, and increase 2+ in IP3 and intracellular [Ca ]. 3. Drugs that act on the ANS (Table 2-3) D. Effects of the ANS on various organ systems (Table 2-4) table 2-3 Prototypes of Drugs that Affect Autonomic Activity Type of Receptor Agonist Antagonist Adrenergic α 1 Norepinephrine Phenoxybenzamine Phenylephrine Phentolamine Prazosin α 2 Clonidine Yohimbine β 1 Norepinephrine Propranolol Isoproterenol Metoprolol Dobutamine β 2 Isoproterenol Propranolol Albuterol Butoxamine Cholinergic Nicotinic ACh Curare Nicotine Hexamethonium (ganglion, but Carbachol not neuromuscular junction) Muscarinic ACh Atropine Muscarine Carbachol ACh = acetylcholine. 98761_Ch02_Chapter 02 5/7/10 6:32 PM Page 35 Chapter 2 Neurophysiology 35 table 2-4 Effect of the Autonomic Nervous System on Organ Systems Organ Sympathetic Sympathetic Parasympathetic Parasympathetic Action Receptor Action Receptor ↑ β ↓ Heart heart rate 1 heart rate M2 ↑ β ↓ contractility 1 contractility (atria) M2 ↑ β ↓ AV node conduction 1 AV node conduction M2 α Vascular smooth Constricts blood vessels 1 — muscle in skin; splanchnic β Dilates blood vessels in 2 — skeletal muscle ↓ α β ↑ Gastrointestinal tract motility 2, 2 motility M3 α Constricts sphincters 1 Relaxes sphincters M3 β Bronchioles Dilates bronchiolar 2 Constricts bronchiolar M3 smooth muscle smooth muscle Male sex organs Ejaculation α Erection M β Bladder Relaxes bladder wall 2 Contracts bladder wall M3 α Constricts sphincter 1 Relaxes sphincter M3 Sweat glands ↑ sweating M (sympathetic — cholinergic) Eye α Radial muscle, iris Dilates pupil (mydriasis) 1 — Circular sphincter — Constricts pupil (miosis) M muscle, iris Ciliary muscle Dilates (far vision) β Contracts (near vision) M ↑ β Kidney renin secretion 1 — ↑ β Fat cells lipolysis 1 — AV = atrioventricular; M = muscarinic. E. Autonomic centers—brain stem and hypothalamus 1. Medulla ■ Vasomotor center ■ Respiratory center ■ Swallowing, coughing, and vomiting centers 2. Pons ■ Pneumotaxic center 3. Midbrain ■ Micturition center 4. Hypothalamus ■ Temperature regulation center ■ Thirst and food intake regulatory centers II. SENSORY SYSTEMS A. Sensory receptors—general ■ are specialized epithelial cells