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A curious neural control: How do muscarinic receptors in the heart slow down heart rate?
In our daily lives, the speed of our heartbeats seems to be natural, but there is a complex neural control mechanism behind it. Muscarinic acetylcholine receptors (mAChRs) are an important part of this, and they have a profound impact on the functioning of the heart. The presence of these receptors allows the heart to adjust its activity in different situations, such as how to keep the heart rhythm stable during rest or exercise.
Introduction to Muscarinic Receptors
Muscarinic receptors are a type of acetylcholine receptor that are mainly found in the parasympathetic nervous system. These receptors form G protein-coupled receptor complexes in the cell membrane and play key roles in neurons as well as other cells. The characteristic of this type of receptor is that it is more sensitive to muscarine than to nicotine, hence the name. In the autonomic nervous system, they also coexist with nicotinic acetylcholine receptors (nAChRs) and together regulate a variety of physiological processes in the body.
Muscarinic receptors in the heart
In the heart, the function of the M2 muscarinic receptor is particularly important. These receptors are mainly distributed in the sinoatrial node and atrioventricular node of the heart. When acetylcholine binds to them, it causes a decrease in heart rate. Specifically, these receptors reduce the level of cAMP by inhibiting adenylate cyclase, thereby slowing the rate of depolarization of the heart.
Under normal circumstances, the activity of the parasympathetic nervous system dominates that of the sympathetic nervous system, keeping the heart rate within an appropriate range.
Mechanism of action of muscarinic receptors
When the M2 receptor is stimulated by acetylcholine, the receptor's Gi class G protein is activated, which leads to multiple downstream effects. For example, it improves the permeability of cardiac cell membranes to calcium ions, thereby inhibiting the opening of calcium channels and reducing the calcium ion concentration in the heart. Furthermore, this promotes the efflux of potassium ions, further leading to electrophysiological stabilization of the heart.
This neurotransmission process shows that the parasympathetic nervous system plays an irreplaceable role in the regulation of the heart.
Clinical Application and Related Research
Muscarinic receptors are also widely used in modern medicine. Drugs such as atropine and scopolamine achieve their therapeutic effects by modulating these receptors. For example, atropine's antagonism of M2 receptors can increase heart rate, which is important in certain medical emergencies.
Further research suggests that modulation of the Muscarinic receptor may aid in the development of new antipsychotic drugs, particularly in the area of mental health. The approval of the new combined drug KarXT is a breakthrough in this regard, and the mechanism of this drug relies on the action of mAChRs.
SummaryThe mystery of muscarinic receptors is gradually being revealed. They are not just a group of simple receptors, but part of a complex neural network that is responsible for the functioning of the heart. These receptors play a vital role in stabilizing the heartbeat and regulating heart health. Overall, there are still many mysteries waiting to be explored in the study of Muscarinic receptors. How do they affect our daily health and what deeper questions will they raise?
