Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias.
Cocaine is a highly active stimulant that alters dopamine metabolism in the central nervous system resulting in a feeling of euphoria that with time can lead to addictive behaviours. Cocaine has numerous deleterious effects in humans including seizures, vasoconstriction, ischaemia, increased heart rate and blood pressure, cardiac arrhythmias and sudden death. The cardiotoxic effects of cocaine are indirectly mediated by an increase in sympathomimetic stimulation to the heart and coronary vasculature and by a direct effect on the ion channels responsible for maintaining the electrical excitability of the heart. The direct and indirect effects of cocaine work in tandem to disrupt the co-ordinated electrical activity of the heart and have been associated with life-threatening cardiac arrhythmias. This review focuses on the direct effects of cocaine on cardiac ion channels, with particular focus on sodium, potassium and calcium channels, and on the contributions of these channels to cocaine-induced arrhythmias. Companion articles in this edition of the journal examine the epidemiology of cocaine use (Wood & Dargan) and the treatment of cocaine-associated arrhythmias (Hoffmann).
O'Leary
Michael E
ME
Department of Pathology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. michael.oleary@jefferson.edu
Hancox
Jules C
JC
D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D003042:Cocaine / Q000009:adverse effects*; D019970:Cocaine-Related Disorders; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D017202:Myocardial Ischemia / Q000139:chemically induced*
D018765:Dopamine Uptake Inhibitors; D007473:Ion Channels; D003042:Cocaine