Sensitivity of native and cloned hippocampal delayed-rectifier potassium channels to verapamil.
The effects of the phenylalkylamine verapamil on native and cloned hippocampal voltage-operated potassium channels were investigated. Native channels were studied in acutely isolated CA1 neurons from the guinea pig with the whole-cell patch-clamp technique. Cloned channels were expressed in oocytes of Xenopus laevis and studied with the two-electrode voltage-clamp technique. Native potassium channels: Verapamil suppressed the potassium currents in micro- and submicromolar concentrations. The current suppression increased during the voltage step. The IC50 value of verapamil was 3 micromol/l and the Hill coefficient was 0.5 indicating a mixed population of potassium channels with distinct verapamil sensitivity. Cloned potassium channels: The hippocampal potassium channels Kv1.1, Kv1.2, Kv1.3, Kv2.1, Kv3.1 and Kv3.2 were affected by verapamil in micromolar concentrations. The effect increased with depolarization time, was voltage-dependent, reached 90% of the maximum within around 40 s after start of verapamil application, recovered slowly after wash-out and did not reach control values even after wash-out times of six minutes. The IC50 values differed markedly and were 35 micromol/l for the Kv1.1 channel, 98 micromol/l for the Kv1.2 channel, 12 micromol/l for the Kv1.3 channel, 226 micromol/l for the Kv2.1 channel, 6 micromol/l for the Kv3.1 channel and 11 micromol/l for the Kv3.2 channel.
Madeja
M
M
Institut für Physiologie, Münster, Germany. madeja@uni-muenster.de
Müller
V
V
Musshoff
U
U
Speckmann
E J
EJ
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D051668:Delayed Rectifier Potassium Channels; D004594:Electrophysiology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D051669:Shab Potassium Channels; D014700:Verapamil / Q000494:pharmacology*; D014982:Xenopus laevis
D002121:Calcium Channel Blockers; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D051669:Shab Potassium Channels; D014700:Verapamil