Short communication Inhibition of voltage-gated K channels and Ca channels by diphenidol

Background: Although diphenidol has long been deployed as an anti-emetic and anti-vertigo drug, its mechanism of action remains unclear. In particular, little is known as to how diphenidol affects neuronal ion channels. Recently, we showed that diphenidol blocked neuronal voltage-gated Na+ channels, causing spinal blockade of motor function, proprioception and nociception in rats. In this work, we investigated whether diphenidol could also affect voltage-gated K+ and Ca2+ channels. Methods: Electrophysiological experiments were performed to study ion channel activities in two neuronal cell lines, namely, neuroblastoma N2A cells and differentiated NG108-15 cells. Results: Diphenidol inhibited voltage-gated K+ channels and Ca2+ channels, but did not affect store-operated Ca2+ channels. Conclusion: Diphenidol is a non-specific inhibitor of voltage-gated ion channels in neuronal cells.