Which of the follow ing Physiological Function is mediated by Acetylcholine through Nicotinic receptors?
Correct Answer: Contraction of skeletal muscle
Description: (D) Contraction of skeletal muscle# Historically, Acetylcholine Receptors have been divided into two main types on the basis of their pharmacologic properties.> Muscarine, the alkaloid responsible for the toxicity of toadstools, has little effect on the receptors in autonomic ganglia but mimics the stimulatory action of acetylcholine on smooth muscle and glands. These actions of acetylcholine are therefore called muscarinic actions, and the receptors involved are muscarinic cholinergic receptors.> They are blocked by the drug atropine. In sympathetic ganglia, small amounts of acetylcholine stimulate postganglionic neurons and large amounts block transmission of impulses from pre- to postganglionic neurons. These actions are unaffected by atropine but mimicked by nicotine.> Consequently, these actions of acetylcholine are nicotinic actions and the receptors are nicotinic cholinergic receptors. Nicotinic receptors are subdivided into those found in muscle at neuromuscular junctions and those found in autonomic ganglia and the central nervous system. Both muscarinic and nicotinic acetylcholine receptors are found in large numbers in the brain.> The nicotinic acetylcholine receptors are members of a superfamily of ligand-gated ion channels that also includes the GABAA and glycine receptors and some of the glutamate receptors. They are made up of multiple subunits coded by different genes.> Each nicotinic cholinergic receptor is made up of five subunits that form a central channel which, when the receptor is activated, permits the passage of Na+ and other cations. The five subunits came from a menu of 16 known subunits, a1-a9, b2-b5, g, d, and e, coded by 16 different genes. Some of the receptors are homomeric, eg, those that contain five a7 subunits, but most are heteromeric.> The muscle type nicotinic receptor found in the fetus is made up of two a1 subunits, a b1 subunit, an a subunit, and a d subunit. In adult mammals, the d subunit is replaced by an z subunit, which decreases the channel open time but increases its conductance.> The nicotinic cholinergic receptors in autonomic ganglia are heteromers that usually contain a3 subunits in combination with others, and the nicotinic receptors in the brain are made up of many other subunits.> Many of the nicotinic cholinergic receptors in the brain are located presynaptically on glutamine-secreting axon terminals, and they facilitate the release of this transmitter. However, others are postsynaptic. Some are located on structures other than neurons, and some seem to be free in the interstitial fluid, ie, they are perisynaptic in location.> There is a binding site for acetylcholine on each a subunit, and when an acetylcholine molecule binds to each of them, they induce a configurational change in the protein so that the channel opens. This increases the conductance of Na+ and other cations, and the resulting influx of Na+ produces a depolarizing potential.> A prominent feature of neuronal nicotinic cholinergic receptors is their high permeability to Ca2+, suggesting their involvement in synaptic facilitation and learning.> Muscarinic cholinergic receptors are very different from nicotinic cholinergic receptors. Five types, encoded by five separate genes, have been cloned. The exact status of M5 is uncertain, but the remaining four all are serpentine receptors coupled via G proteins to adenylyl cyclase, K+ channels, or phospholipase C.> The nomenclature of these receptors has not been standardized, but the receptor designated M1 is abundant in the brain.> The M2 receptor is found in the heart. The M4 receptor is found in pancreatic acinar and islet tissue, where it mediates increased secretion of pancreatic enzymes and insulin. The M3 and M4 receptors are both found in smooth muscle.
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