Physiological and other biological pacemakers

Abstract

Physiological pacemaking in the heart is the province of the sinus node, in which transmembrane ionic currents and Ca2+ homeostasis mechanisms interact to generate the pacemaker potential. A key transmembrane component for initiating pacemaker function is If, an inward current carried by sodium through a family of channels that are hyperpolarization-activated and cyclic nucleotide-gated (HCN channels). In many settings where physiological pacemaking fails, therapy involves electronic pacing. Because of shortcomings in this otherwise excellent technology, there has been a search for biological alternatives in which either gene or cell therapy is used to decrease outward current or increase inward current to provide pacemaker function. The various technologies used are summarized in the following pages as are directions for optimizing biological pacemaker function and for using them in tandem with electronic units.