Sustained inward current during pacemaker depolarization in mammalian sinoatrial node cells

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 spontaneo us action potentials can be reconstructed by incorporating these currents, but relative contributions of individual currents vary widely between diffe rent models. in 1995, the presence of a novel inward current that was activ ated by depolarization to the potential range of the slow diastolic depolar ization in rabbit sinoatrial (SA) node cells was reported. Because the curr ent showed little inactivation during depolarizing pulses, it was called th e sustained inward current (I-st). A similar current is also found in SA no de cells of the guinea pig and rat and in subsidiary pacemaker atrioventric ular node cells. Recently, single-channel analysis has revealed a nicardipi ne-sensitive, 13-pS Na+ current, which is activated by depolarization to th e diastolic potential range in guinea pig SA node cells. This channel diffe rs from rapid voltage-gated Na+ or L-type Ca2+ channels both in unitary con ductance and gating kinetics. Because I-st was observed only in spontaneous ly beating SA node cells, ie, it was absent in quiescent cells dissociated from the same SA. or atrioventricular node, an important role of I-st for g eneration of intrinsic cardiac automaticity was suggested.