Muscarinic receptors are those membrane bound acetylcholine receptors that are more sensitive to muscarine than nicotine. Those for which the contrary is true are known as nicotinic acetylcholine receptors. Muscarine and nicotine are both alkaloids. Many drugs and other substances (for example atropine, scopolamine) act as agonists or antagonists of only muscarinic or only nicotinic receptors, making this distinciton useful.

Context

Acetylcholine receptors, of which muscarinic receptors are a subdivision, are widely distributed in the autonomic nervous system. The autonomic nervous system is anatomically distinct from the voluntary nervous system. The autonomic nervous system controls various involuntary actions, such as heart rate, pupil dilation, sweating, salivation, urination and defecation, digestion, and so on. Though these actions are known as 'involuntary', that is not to say that the concious mind is unaware of these actions, or unable to influence them. It is the autonomic nervous system about which the most is known concerning muscarinic receptors.

The autonomic nervous system is divided into two parts, the sympathetic and the parasympathetic nervous systems. The sympathetic nervous system is responsible for sweating, bronchodilation, increased heart-rate and blood pressure, decreased digestion, and so on, (often summaraised as flight or fight) whereas the parasympathetic nervous system is responsible for salivation, decreased heart-rate, the accomodation of the eye for near-work, digestion, and so on (often summarised as rest and digest). The distribution of muscarinic receptors crucially differs between the sympathetic and the parasympathetic nervous system, a full discussion of which follows.

A further necessary distinction to make in our desctiption of muscarinic receptors is that, in contrast to the voluntary nervous system -- which consists of a single nerve cell extending from the central nervous system to the synapse between that nerve and the innervated organ -- the autonomic nervous system consists of two nerve cells. The junction between these cells is a ganglion, usually located in or near the target organ. The nerve extending from the cns to the ganlion is known as the preganglionic neurone. The nerve extending form the ganglion to the innervated tissue is known as the postganglionic neurone.

Physiology

Acetylcholine (ACh) is used as a neurotransmitter within the autonomic nervous system.

ACh is always used as the transmitter within the autonomic ganglion. nicotinic receptors on the postganglionic neuron are responsible for the initial fast depolarisation (Fast EPSP) of that neurone. As a consequence of this, nicotinic receptors are often cited as the receptor on the postganglionic neurone at the ganglion. However, the subsequent hyperpolarisation (IPSP) and slow depolarisation (Slow EPSP) which represent the recovery of the postganglionic neuron from stimulation are actually mediated by muscarinic receptors, types M2 and M1 respectively (discussed later).

Another role for these receptors is at the junction of the innervated tissue and the postganglionic neuron in the parasympathetic division of the autonomic nervous system. Here acetylcholine is again used as a neurotransmitter, and muscarinic receptors form the principal receptors on the innervated tissue. In addition, muscinaric acetylcholine receptors pre-synaptically on the post-ganglionic neuron bind to the released acetylcholine and regulate the response of the postganglionic neurone.

By contrast, this junction in the sympathetic division does not tend to use acetylcholine as a neurotransmitter, and therefore neither muscarinic nor nicotinic receptors are involved. A very few parts of the sympathetic system (sweating, for example), do use acetylcholine as a neurotransmitter at this position. In these cases, the receptors are of the muscarinic type. The sympathetic nervous system also has single nerves terminating at the adrenal medula, which can secrete adrenaline into the bloodstream. Acetylcholine is used as a neurotransmitter, and the receptor is of the nicotinic type. The voluntary nervous system uses acetylcholine at the junction between its one peripheral nerve and the innervated tissue, also of the nicotnic type.

Muscinaric acetylcholine receptors are also present distributed throughout the central nervous system, in post-synaptic and pre-synaptic postions.

In summary then, muscinaric receptors can be found

Between the postganglionic neurone and the innervated tissue throughout the parasympathetic nervous system.
Presynaptically within the postganglionic neurone to regulate acetylcholine release in the parasympathetic nervous system.
Between the postganglionic neurone and the innervated tissue in a very few parts of the sympathetic nervous system.
Within the ganglions of the whole autonomic nervous system (sympathetic and parasympathetic), acting as recovery receptors after the primary stimulation of the postganglionic neurone by action on nicotinic receptors by ACh from the preganglionic neurone.
In various parts of the higher central nervous system, which are currently poorly characterised, but have a role in cognition and memory, and degenerate in Alzheimer's disease.

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Five subtypes of muscarinic receptors have been found, designated M₁ through M₅.

M₁: These receptors are found in autonomic ganglia. Presynaptic receptors act as autoreceptors to regulate acetylcholine release through negative feedback mechanisms. Postsynaptic receptors on sympathetic neurons allow the parasympathetic nervous system to inhibit sympathetic effects.

M₂: These receptors are found in cardiac tissue and cause a slowing of sinoatrial depolarization and a decrease in conduction velocity.

M₃: These receptors are found on smooth muscles and in glands. M₃ receptors generally cause smooth muscle contraction and increased glandular secretions.