At the peak of the action potential upstroke, a short rapid period of repolarization occurs and the membrane potential returns toward 0 mV. This produces a spike and dome configuration of the action potential and is a result of the inactivation of the INa and activation of a short-lived outward current called the transient outward current (Ito). Ito is composed of two distinct channels carried by either potassium or chloride. The distribution of Ito is heterogeneous throughout the myocardium and varies from species to species. Ito is present in both the atrium and the ventricular myocardium. Within the ventricle, Ito is present in the epicardium and absent in the endocardium. Consequently, the epicardium repolarizes more rapidly than the endocardium; this is the basis for the QRS complex and the T-wave on the surface electrocardiogram having an identical axis as opposed to an opposite axis. Abnormalities in the function of Ito have been implicated in Brugada syndrome, a potentially lethal genetic disease resulting in ventricular tachycardia and fibrillation.

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