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 Ca 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, which is activated by depolarization to the diastolic potential range in guinea pig SA node cells. This channel differs from rapid voltage-gated Na or L-type Ca channels both in unitary conductance and gating kinetics. Because Ist was observed only in spontaneously beating SA node cells, ie, it was absent in quiescent cells dissociated from the same SA or atrioventricular node, an important role of Ist for generation of intrinsic cardiac automaticity was suggested. (Circ Res. 2000;87:88-91.)