Cocaine-induced inhibition of ATP-sensitive K+ channels in rat ventricular myocytes and in heart-derived H9c2 cells.
Cocaine use may cause coronary artery spasm and acute myocardial ischaemia/infarction. However, its effects on ATP-sensitive K+ (KATP) channel, an ion channel responsible for ischaemic preconditioning, remain unknown. In isolated rat ventricular myocytes with whole-cell experiments, cocaine can reverse action potential shortening and increased K+ current caused by the openers of ATP-sensitive K+ (KATP) channels. In inside-out patches, cocaine applied to intracellular surface suppressed KATP-channel activity in a concentration-dependent manner with an IC50 value of 9.2 microM; however, it did not modify the single-channel conductance of this channel. The change in the kinetic behaviour of KATP channels caused by cocaine is primarily the result of an increase in mean closed time and a decrease in mean open time. Cocaine-induced inhibition of KATP channels is independent of change in intracellular ATP concentrations. In heart-derived H9c2 cells, cocaine is also capable of suppressing KATP-channel activity. The present study provides evidence that cocaine can produce a depressant action on KATP channels in cardiac myocytes, and thus disturb ischaemic preconditioning in clinical settings.
Wu
Sheng-Nan
SN
Department of Physiology, National Cheng Kung University Hospital, Tainan, Taiwan.
Chang
Hang-Dong
HD
Sung
Ruey J
RJ
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015640:Ion Channel Gating; D007700:Kinetics; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D020110:Pinacidil; D000255:Adenosine Triphosphate; D003042:Cocaine; D011188:Potassium