Block by a putative antiarrhythmic agent of a calcium-dependent potassium channel in cultured hippocampal neurons.
The actions of a new, putative antiarrhythmic drug, KC-8851 on single channel currents in hippocampal CA1 neurons have been studied. A calcium-dependent potassium current IK(Ca) was activated in the cultured neurons when a solution containing 140 mM K+ and 0.2 mM Ca2+ was applied to inside-out patches. Addition of the compound KC-8851, at concentrations between 1-50 microM, resulted in significant, dose-dependent, decreases in the mean open times of the K channel. The onward (blocking) rate constant was determined from a simple channel blockade scheme and was 5 x 10(7) M-1s-1; this rate constant was not dependent on voltage. Addition of KC-8851 to the solution bath with outside-out patches also caused significant decreases in the mean open times of the IK(Ca) channel consistent with channel blockade by the drug.
McLarnon
J G
JG
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D003521:Cyclopropanes; D015221:Potassium Channels; C059921:tedisamil; D002118:Calcium