Tedisamil blocks a calcium-dependent potassium channel in cultured motoneurons.
A calcium-dependent potassium channel K(Ca) has been isolated in mouse motoneurons. With physiological concentrations of potassium across inside-out patches, a 100 pS K(Ca) channel was activated when the bath solution of Ca2+ was in excess of 1 microM. Introduction of the drug tedisamil, a blocker of repolarizing potassium channels in cardiac cells, at concentrations in the range 0.2-10 microM, caused a dose-dependent decrease in the mean open times for K(Ca). The drug action was consistent with open channel block of K(Ca) with an onward (blocking) rate constant of 6 x 10(7) M-1 s-1. Tedisamil, at concentrations of 1 microM and 5 microM, also blocked the K(Ca) channel when applied to outside-out patches with a similar potency as found with internal application. A large conductance K(Ca) channel in hippocampal neurons is also blocked by a number of putative Class III antiarrhythmic drugs, including tedisamil; thus, these agents may have utility in the characterization of the properties of K(Ca) channels in various cells.
McLarnon
J G
JG
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Sawyer
D
D
Michikawa
M
M
Kim
S U
SU
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003521:Cyclopropanes / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009431:Neural Conduction / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011247:Pregnancy; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; D015221:Potassium Channels; C059921:tedisamil; D002118:Calcium