General features | Nervous system and special senses | Physiology

General features of the sympathetic nervous system: All preganglionic neurons release acetylcholine (ACh) as a neurotransmitter. Most postganglionic neurons release norepinephrine (NE) while some release ACh. Sympathetic ganglia are located in prevertebral and paravertebral ganglia. ACh released from the preganglionic sympathetic neurons acts on nicotinic receptors on the ganglia. The postganglionic sympathetic receptors are of different types - alpha1 and 2 and beta 1,2 and 3. The sympathetic postganglionic nerve terminals have vesicles containing NE and neuropeptide Y and ATP. The adrenal medulla, which is a specialized sympathetic ganglion releases mainly epinephrine and a smaller amount of NE when it is stimulated. Postganglionic fibres travel in the spinal nerves. Most arterioles and veins receive solely sympathetic innervation.

General features of the parasympathetic nervous system: Parasympathetic ganglia are situated close to the effector organs. Preganglionic as well as postganglionic parasympathetic neurons release ACh. Nicotinic (N) receptors are present on the ganglia while muscarinic (M) receptors are located on the effector organs. Nicotinic acetylcholine receptors are pentameric ligand-gated ion channels, whereas muscarinic acetylcholine receptors are seven-helix G-protein coupled membrane proteins. In some cases, vasoactive intestinal peptide, nitric oxide etc are released by the parasympathetic nerve terminals.

Sodium channel in nervous tissue: The voltage gated sodium channel is present in high concentrations in the neuronal cells and axons in the CNS and PNS. It is coded by the SCN gene. It is composed of alpha and beta subunits. Depending on the variability of the alpha subunit, there are 10 types of sodium channels. The alpha subunit is made of four transmembrane domains - DI-IV, three intracellular loops and the C and N terminus. Each transmembrane domain is comprised of 6 alpha helical transmembrane segments S1-6. Arginine containing segment S4 is the voltage sensor. The S6 segment of domain IV has been proposed to contain the receptor for local anaesthetics, which block Na+ channels in a voltage-dependent manner.

The channel has a pore for sodium ions to pass and is guarded by two gates - a fast, activation or “m” gate and a slow, inactivation or “h” gate. Depolarization causes the activation gate to open allowing sodium to enter the cell. At rest, the activation gate is closed while the inactivation gate is open, technically closing off the channel. At the peak of the action potential, the inactivation gate closes thus initiating repolarization and going back to the resting state.

Receptors in the autonomic nervous system: Receptors bind to neurotransmitters and mediate their tissue effects. As each receptor family has different effector mechanisms the same neurotransmitter will have different effects on different tissues.

Sympathetic receptors

Receptor type	Target tissue	Mechanism of action	Effects
Alpha 1	Contraction of smooth muscle in blood vessels and sphincters of the GIT, genitourinary system, bladder sphincter, skin and radial muscle of iris.	Activates Gq and phospholipase C, increased intracellular levels of IP3 and DAG, Calcium	Increased blood pressure, glycogenolysis, gluconeogenesis, urinary retention, piloerection, sodium reabsorption from the kidneys, dilation of the pupil, sweating.
Alpha 2	Presynaptic adrenergic nerve terminal, GIT	Activates Gi protein, inhibits adenylate cyclase, decreases cAMP.	Negative feedback inhibition, decreases insulin release, increases glucagon release, platelet aggregation.
Beta 1	Heart, juxtaglomerular cells of the kidney, adipose tissue, salivary glands	Activates Gs protein, activates adenylate cyclase, increases cAMP.	Increases heart rate, contractility, conduction velocity, increases renin secretion.
Beta 2	Smooth muscle in the bronchioles, GIT, veins, blood vessels in skeletal muscle, uterus, GIT sphincters, salivary glands, mast cells, detrusor muscle, adipose tissue, trabecular cells of the eye, iris and ciliary body	Activates Gs protein, activates adenylate cyclase, increases cAMP.	Bronchodilation, lipolysis, glycogenolysis, gluconeogenesis, urinary retention, increased insulin secretion, releases histamine from mast cells, vasodilation in skeletal muscle, relaxation of uterus.
Beta 3	Adipose tissue, urinary bladder.	Activates Gs protein, activates adenylate cyclase, increases cAMP.	Lipolysis, urinary retention, nonshivering thermogenesis in brown fat.

Parasympathetic receptors

Receptor type	Target tissue	Mechanism of action	Effects
M1	Exocrine glands, parietal cells of stomach, CNS, enteric nervous system.	Activates Gq and phospholipase C, increased intracellular levels of IP3 and DAG, Calcium	Cognition, memory, increased gastric acid secretion
M2	Heart, airways (postganglionic cholinergic nerves)	Activates Gi protein, inhibits adenylate cyclase, decreases cAMP, inhibition of voltage gated calcium channels.	Reduce heart rate, reduced conduction at the AV node, reduced contractility; inhibit ACh release in airways.
M3	Smooth muscle of blood vessels, lungs, glands, urinary bladder, eye,GIT	Activates Gq and phospholipase C, increased intracellular levels of IP3 and DAG, Calcium	Bronchoconstriction, increased glandular secretion, increased insulin release, bladder contraction, miosis, accommodation of eye, increased GIT motility, increased synthesis of nitric oxide, vasodilation.
M4	CNS	Activates Gi protein, inhibits adenylate cyclase, decreases cAMP, inhibition of voltage gated calcium channels.	Inhibition of ACh release by feedback inhibition.
M5	CNS especially substantia nigra and nigrostriatal pathway	Activates Gq and phospholipase C, increased intracellular levels of IP3 and DAG, Calcium	Not clear, under research.
Nm	Neuromuscular junction	Opening of sodium and potassium channels	Muscle contraction
Nn	Autonomic ganglia, chromaffin cells of the adrenal medulla	Opening of sodium and potassium channels	Release of adrenal hormones, mediate fast synaptic transmission in ganglia, regulation of autonomic activity.

Nicotinic receptors, Nn as well as Nm type, have 5 subunits - two alpha, one each of beta, delta and epsilon. The alpha subunits have the ACh binding site. Both sites should be bound to open the ion channel. Activation causes influx of sodium and calcium and efflux of potassium.