Premium
Cocaine‐Induced Inhibition of ATP‐Sensitive K + Channels in Rat Ventricular Myocytes and in Heart‐Derived H9c2 Cells
Author(s) -
Wu ShengNan,
Chang HangDong,
Sung Ruey J.
Publication year - 2006
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2006.pto_354.x
Subject(s) - myocyte , medicine , chemistry , pharmacology , cardiology , biophysics , biology
Cocaine use may cause coronary artery spasm and acute myocardial ischaemia/infarction. However, its effects on ATP‐sensitive K + (K ATP ) 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 + (K ATP ) channels. In inside‐out patches, cocaine applied to intracellular surface suppressed K ATP ‐channel activity in a concentration‐dependent manner with an IC 50 value of 9.2 μM; however, it did not modify the single‐channel conductance of this channel. The change in the kinetic behaviour of K ATP 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 K ATP channels is independent of change in intracellular ATP concentrations. In heart‐derived H9c2 cells, cocaine is also capable of suppressing K ATP ‐channel activity. The present study provides evidence that cocaine can produce a depressant action on K ATP channels in cardiac myocytes, and thus disturb ischaemic preconditioning in clinical settings.