Na/H Exchange and Arrhythmia

Summary

The Na/H exchanger is a transporter protein embedded in the plasma membrane, extruding H in exchange for extracellular Na using a high concentration gradient of Na existing across the plasma membrane, which is high in the extracellular space. This transporter functions as a controller of intracellular pH in the face of continual production of H especially in the setting of cellular ischemia and anaerobic metabolism. Myocytes have isozyme 1 and during ischemia/reperfusion when the H suddenly accumulates, this is followed by Na increases intracellularly, inducing Ca overload via activation of Na/Ca exchangers. Recently selective Na/H exchange inhibitors such as cariporide have been developed. These drugs have been shown to protect against ischemic myocardial damage in various experimental models, including coronary ischemia/reperfusion ventricular arrhythmias. These drugs, unlike beta blockers, Ca antagonists, Na channel blockers etc, are effective even given after the start of ischemia, or given simultaneously with reperfusion, and large scale clinical trials have been presently undertaken.