General Characteristics and M1 Receptors
Muscarinic acetylcholine receptors are predominantly located on the postsynaptic membrane of effector organs innervated by postganglionic parasympathetic fiber terminals. Several main subtypes are distinguished based on their localization and resulting effects.
| Subtype | Main Localization | Key Effect |
|---|---|---|
| M1 | CNS, stomach (ECL cells) | Neuronal transmission, stimulation of HCl production |
| M2 | Heart, presynaptic membrane | Cardiac inhibition, suppression of neurotransmitter release |
| M3 (innervated) | Smooth muscle, exocrine glands, eye | Muscle contraction, profuse glandular secretion |
| M3 (non-innervated) | Vascular endothelium | Blood vessel dilation (vasodilation) |
M1 receptors are diffusely distributed in cholinergic synapses of the central nervous system (cortex, brainstem, midbrain, and spinal cord), where they mediate neuronal transmission.
Their crucial peripheral function is the regulation of gastric secretion. In the stomach, they are located on enterochromaffin-like (ECL) cells. These receptors are coupled with Gq proteins, and their stimulation increases cytoplasmic calcium ion (Ca²⁺) levels. This triggers a cascade: ECL cells release histamine, which secondarily stimulates gastric parietal cells to actively secrete hydrochloric acid (HCl).
M2 Receptors: Regulation of Cardiac Function
These receptors are traditionally referred to as 'cardiac' receptors. Their primary function is the inhibition of cardiac activity through specific ionic mechanisms. Upon M2 receptor stimulation, potassium channels are activated, leading to an enhanced efflux of K⁺ ions and membrane hyperpolarization. Simultaneously, phosphorylation of calcium channels decreases, reducing Ca²⁺ influx into cardiomyocytes during depolarization.
Effects on cardiac regions:
- Sinoatrial (SA) node: Spontaneous diastolic depolarization slows down, decreasing automaticity and, consequently, heart rate (negative chronotropic effect).
- Atria: Contractility decreases (negative inotropic effect), the refractory period shortens, and impulse conduction velocity through the atria decreases.
- Atrioventricular (AV) node: Conduction velocity slows down and the refractory period lengthens (negative dromotropic effect).
- Ventricles: Contractility decreases only slightly, as parasympathetic innervation is sparse in this region.
In addition to the heart, M2 receptors have a presynaptic localization on the membranes of postganglionic parasympathetic nerve terminals. Their excitation triggers a negative feedback mechanism that inhibits the release of the neurotransmitter (acetylcholine) into the synaptic cleft.
M3 Receptors: Smooth Muscle, Glands, and Blood Vessels
Innervated M3 receptors represent the largest group, mediating classical parasympathetic effects. Their molecular mechanism also involves Gq proteins: activation of phospholipase C leads to the production of inositol 1,4,5-trisphosphate, the release of Ca²⁺ ions from the sarcoplasmic reticulum, and an increase in cytoplasmic calcium concentration.
Main targets of M3 receptors:
- Eye: Contraction of the circular muscle of the iris (resulting in pupil constriction — miosis) and the ciliary muscle (causing accommodation spasm, adjusting the eye for near vision).
- Smooth muscle of internal organs: Tone increases (except for sphincters), and motility is enhanced in the bronchi, stomach, intestines, biliary tract, uterus, and urinary bladder.
- Exocrine glands: A generalized increase in secretion is observed (salivary, lacrimal, bronchial, gastric, sweat, nasopharyngeal, and intestinal glands).
A special subtype is the non-innervated M3 receptor. These lack synaptic connections with nerve endings, are localized on vascular endothelial cells, and respond to circulating agonists in the bloodstream. Stimulation of these receptors leads to the synthesis and release of endothelium-derived relaxing factor (nitric oxide, NO). NO diffuses into the smooth muscle cells of the vessel wall, causing them to relax. As a result, vasodilation occurs and arterial blood pressure decreases.