title: The Inhibitory Effects of Ca2+ Channel Blocker Nifedipine on Rat Kv2.1 Potassium Channels.
abstract: It is well documented that nifedipine, a commonly used dihydropyridine Ca2+ channel blocker, has also significant interactions with voltage-gated K+ (Kv) channels. But to date, little is known whether nifedipine exerted an action on Kv2.1 channels, a member of the Shab subfamily with slow inactivation. In the present study, we explored the effects of nifedipine on rat Kv2.1 channels expressed in HEK293 cells. Data from whole-cell recording showed that nifedipine substantially reduced Kv2.1 currents with the IC50 value of 37.5 ± 5.7 μM and delayed the time course of activation without effects on the activation curve. Moreover, this drug also significantly shortened the duration of inactivation and deactivation of Kv2.1 currents in a voltage-dependent manner. Interestingly, the half-maximum inactivation potential (V1/2) of Kv2.1 currents was -11.4 ± 0.9 mV in control and became -38.5 ± 0.4 mV after application of 50 μM nifedipine. The large hyperpolarizing shift (27 mV) of the inactivation curve has not been reported previously and may result in more inactivation for outward delayed rectifier K+ currents mediated by Kv2.1 channels at repolarization phases. The Y380R mutant significantly increased the binding affinity of nifedipine to Kv2.1 channels, suggesting an interaction of nifedipine with the outer mouth region of this channel. The data present here will be helpful to understand the diverse effects exerted by nifedipine on various Kv channels.
authors.affiliation: Department of Neuroscience, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.
authors.forename: Xian-Tao
authors.initials: XT
authors.lastname: Li
authors.affiliation: Department of Neuroscience, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Li
authors.affiliation: South-Central University for Nationalities, Wuhan, China.
authors.forename: Xi-Mu
authors.initials: XM
authors.lastname: Hu
authors.affiliation: South-Central University for Nationalities, Wuhan, China.
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D015640:Ion Channel Gating; D050505:Mutant Proteins / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D010957:Plasmids / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D050505:Mutant Proteins; D051669:Shab Potassium Channels; D009543:Nifedipine; D011188:Potassium