Sustained Inward Current During Pacemaker Depolarization in Mammalian Sinoatrial Node Cells

Abstract—Several time- and voltage-dependent ionic currents have been identified in cardiac pacemaker cells, including Na+ current, L- and T-type Ca2+ currents, hyperpolarization-activated cation current, and various types of delayed rectifier K+ currents. Mathematical models have demonstrated that spontaneous action potentials can be reconstructed by incorporating these currents, but relative contributions of individual currents vary widely between different models. In 1995, the presence of a novel inward current that was activated by depolarization to the potential range of the slow diastolic depolarization in rabbit sinoatrial (SA) node cells was reported. Because the current showed little inactivation during depolarizing pulses, it was called the sustained inward current (Ist). A similar current is also found in SA node cells of the guinea pig and rat and in subsidiary pacemaker atrioventricular node cells. Recently, single-channel analysis has revealed a nicardipine-sensitive, 13-pS Na+ current, whic...