External nickel blocks human Kv1.5 channels stably expressed in CHO cells.
We have investigated the actions of Nickel (Ni(2+)) on a human cardiac potassium channel (hKv1.5), the main component of human atrial ultra-rapid delayed rectifier current, stably expressed in Chinese hamster ovary cell line using the whole-cell voltage-clamp technique. External Ni(2+) reversibly decreased the amplitude of the current in a concentration-dependent manner. The concentration for half-maximum inhibition of the current at +50 mV was 568 microm. The activation, deactivation, reactivation kinetics of the current were not affected by Ni(2+). Block was not voltage-dependent but frequency-dependent block was apparent. The extent of channel block during the first pulse increased when the duration of exposure to Ni(2+), prior to channel activation, was prolonged indicating that Ni(2+) interacted with hKv1.5 in the closed state. The percentage of current remaining in presence of Ni(2+) decreased steeply over the range of steady-state channel inactivation, consistent with an enhanced block with increased inactivation. This suggests that Ni(2+) preferentially blocks nonconducting hKv1.5 channels, either in the resting or inactivated state in a concentration-dependent manner. The data indicate that the mechanisms of hKv1.5 channel inhibition by Ni(2+) are distinct from those of other K(+) channels.
Perchenet
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Preclinical Research, Department of Vascular and Metabolic Diseases, F. Hoffmann-La-Roche Ltd., PRBM, Bau 70/423, Grenzacherstr. 124, CH-4070 Basel, Switzerland.
Clément-Chomienne
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D000818:Animals; D016466:CHO Cells; D002413:Cations, Divalent; D006224:Cricetinae; D004553:Electric Conductivity; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D051666:Kv1.5 Potassium Channel; D009532:Nickel / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated
D002413:Cations, Divalent; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D009532:Nickel