Molecular Basis of the Delayed Rectifier Current IKsin Heart

J. Kurokawa, H. Abriel and R. S. Kass. Molecular Basis of the Delayed Rectifier Current IKsin Heart. Journal of Molecular and Cellular Cardiology (2001) 33, 873–882. Electrical activity underlies the control of the frequency, strength, and duration of contraction of the heart. During the cardiac cycle, a regular rhythmic pattern must be established in time-dependent changes in ionic conductances in order to ensure events that underlie normal cardiac function. This pattern must be tightly regulated by sympathetic nervous activity to ensure a physiologically relevant relationship between diastolic filling and ejection times with variable heart rate. The duration of the ventricular action potential is controlled in part by a slowly activated potassium channel current, IKs. The molecular identity of the subunits that comprise the channels conducting this current is important, not only for understanding the fundamental mechanisms that control electrical activity in healthy individuals, but also for understanding the molecular basis of at least one inherited human disease, LQTS-1. This brief review summarizes key points of information regarding the molecular determinants of the activity of these channels, their relationship to human disease, and what is known, and yet to be discovered, about the molecular determinants of the regulation of this channel by sympathetic nervous activity.