Inhibition of voltage-gated K+ channels and Ca2+ 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 Ca(2+) 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 Ca(2+) channels, but did not affect store-operated Ca(2+) channels.


CONCLUSIONS
Diphenidol is a non-specific inhibitor of voltage-gated ion channels in neuronal cells.
Graduate Institute of Neural and Cognitive Sciences, China Medical University, Taichung 40402, Taiwan. thcheng@mail.cmu.edu.tw
Yuk-Man
YM
Leung
Kar-Lok
KL
Wong
Ka-Shun
KS
Cheng
Chang-Shin
CS
Kuo
Tzu-Hui
TH
Su
Yu-Wen
YW
Chen
Tzu-Hurng
TH
Cheng
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D055724:Electrophysiological Phenomena; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors*
D000932:Antiemetics; D015220:Calcium Channels; D010880:Piperidines; D024642:Potassium Channels, Voltage-Gated; C004858:diphenidol