The Sackler School of Medicine, Department of Physiology and Pharmacology, and Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 69978, Israel.
Int J Mol Sci. 2023 Apr 19;24(8):7538. doi: 10.3390/ijms24087538.
Unexpectedly, the affinity of the seven-transmembrane muscarinic acetylcholine receptors for their agonists is modulated by membrane depolarization. Recent reports attribute this characteristic to an embedded charge movement in the muscarinic receptor, acting as a voltage sensor. However, this explanation is inconsistent with the results of experiments measuring acetylcholine binding to muscarinic receptors in brain synaptoneurosomes. According to these results, the gating of the voltage-dependent sodium channel (VDSC) acts as the voltage sensor, generating activation of Go-proteins in response to membrane depolarization, and this modulates the affinity of muscarinic receptors for their cholinergic agonists.
出乎意料的是，七次跨膜毒蕈碱乙酰胆碱受体与其激动剂的亲和力受膜去极化调节。最近的报告将这一特征归因于毒蕈碱受体中的嵌入电荷运动，充当电压传感器。然而，这一解释与测量脑突触体中毒蕈碱受体乙酰胆碱结合的实验结果不一致。根据这些结果，电压依赖性钠通道 (VDSC) 的门控作用充当电压传感器，对膜去极化产生 Go 蛋白的激活，从而调节毒蕈碱受体对其胆碱能激动剂的亲和力。
