Aim: 

Verapamil is a calcium channel blocker known to affect the function of the muscle endplate acetylcholine receptor (AChR), though its mechanism of action is not fully understood. Yet, a full characterization of the effects of this compound on the endplate AChR may yield therapeutic options for people suffering of rare disorders such as slow-channel congenital myasthenias. This group of diseases results from mutations in subunits of the endplate AChR, which alter channel kinetics, causing abnormally long-lasting channel openings, and hence prolonged synaptic currents, which in turn cause excitotoxic injury of the postsynaptic region by Ca²⁺ overloading.

Methods: 

We therefore investigated the action of verapamil on the functional behaviour of human endplate AChR, expressed by transient transfection in GH4C1 cells, by means of electrophysiological techniques. Both whole-cell and single-channel current responses were examined.

Results: 

Our data show that verapamil affects ACh-evoked currents, although the mechanism of action on wild-type and slow-channel mutant AChR show remarkable differences. However, in the presence of verapamil the kinetics of mutant AChR-channels becomes significantly closer to that of wild-type channels.

Conclusion: 

These findings raise the possibility that verapamil – already widely employed in humans - may be used off-label to treat excitotoxic diseases of the endplate.