PMID: 9435154Jan 22, 1998Paper

Cocaine blockade of the acetylcholine-activated muscarinic K+ channel in ferret cardiac myocytes

The Journal of Pharmacology and Experimental Therapeutics
Y F Xiao, J P Morgan

Abstract

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 on IK(ACh). The concentration to produce 50% inhibition of IK(ACh) was 25 microM and 12 microM 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 as IK(ACh). Furthermore, cocaine inhibited IK(ACh) activated by GTP gamma S, which evokes IK(ACh) by bypassing the muscarinic receptor and directly activating the G-protein, GK. These results suggest that cocaine-induced suppression of IK(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 membra...Continue Reading

Related Concepts

Related Feeds

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.