Are Voltage Sensors Really Embedded in Muscarinic Receptors?

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.

Automated summary

Previous studies suggested that the affinity of seven-transmembrane muscarinic acetylcholine receptors for agonists is influenced by membrane depolarization, but recent reports propose a voltage sensor in the muscarinic receptor. However, experiments measuring acetylcholine binding to muscarinic receptors in brain synaptoneurosomes contradict this explanation. These findings indicate that the voltage-dependent sodium channel (VDSC) acts as the voltage sensor, causing Go-protein activation in response to membrane depolarization, which then modulates the affinity of muscarinic receptors for cholinergic agonists.