RT Journal Article SR Electronic T1 Cocaine Blockade of the Acetylcholine-Activated Muscarinic K+ Channel in Ferret Cardiac Myocytes JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 10 OP 18 VO 284 IS 1 A1 Yong-Fu Xiao A1 James P. Morgan YR 1998 UL http://jpet.aspetjournals.org/content/284/1/10.abstract AB The effects of cocaine on the acetylcholine(ACh)-activated muscarinic K+ current (IK(ACh)) were assessed with the whole-cell patch-clamp technique in single atrial and left ventricular myocytes enzymatically isolated from adult ferret hearts. The density of IK(ACh) is almost 5 times greater in atrial cells than in left ventricular myocytes. Cocaine reversibly blocked IK(ACh) in a dose-dependent manner. Methylecgonidine (MEG), the major product of pyrolysis of cocaine base, also produced similar effects onIK(ACh). The concentration to produce 50% inhibition of IK(ACh) was 25 μM and 12 μM for cocaine and MEG, respectively. Cocaine at micromolar concentrations also significantly inhibited the adenosine-activated purinergic K+ current (IK(Ado)), which has the same electrophysiological properties asIK(ACh). Furthermore, cocaine inhibitedIK(ACh) activated by GTPγS, which evokesIK(ACh) by bypassing the muscarinic receptor and directly activating the G-protein, GK. These results suggest that cocaine-induced suppression ofIK(ACh) is caused by its interactions beyond the binding site of muscarinic receptors. The antimuscarinic effect of cocaine may play an important role in cocaine cardiotoxicity by reducing the membrane electrical stability and acting synergistically with other actions of cocaine to facilitate the occurrence of lethal cardiac arrhythmias. The American Society for Pharmacology and Experimental Therapeutics