“Cardiac K ATP ”

Abstract

Understanding the etiology of and development of appropriate treatment for myocardial ischemia and associated sudden cardiac death is a major goal of cardiovascular research. In a recent review,1 a compelling case is presented that sarcolemmal ATP-sensitive potassium (KATP) channels are an excellent target for antiarrhythmic therapy. Because opening of cardiac KATP channels shortens the action potential and reduces the refractory period, its activation can establish an arrhythmogenic substrate, supporting reentry. Hence, inhibition of KATP could be an ideal way to stop or even prevent arrhythmias: these channels tend to be closed under normal circumstances and to open only when cell metabolism is inhibited; therefore, any agents that inhibit KATP activity should specifically target channels only during ischemia, leaving nonischemic myocardium unaffected. On the other hand, activation of cardiac KATP channels has consistently been shown to protect the heart from damage during ischemia by limiting Ca entry.2 Finding a way to balance these opposing effects on the heart before, during, and after an ischemic event remains an intractable issue. Until recently, efforts to manipulate cardiac KATP have generally been conducted under a single underlying assumption, namely that cardiac KATP channels are structurally and functionally the same throughout the heart. However, recent studies, including the new report of Bao and colleagues3 in this issue, reveal that “cardiac KATP” is not a single entity and is more accurately a collection of structurally distinct channels. The relative density of each one varies regionally in the heart, may differ between species, and may be under dynamic control. Article see p 926 KATP channels are expressed in many different excitable tissues, where they couple cell energetic status with membrane excitability and function.4 In different tissues, KATP channels exhibit different properties. This …