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(Circulation Research. 2000;87:88.)
© 2000 American Heart Association, Inc.

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Sustained Inward Current During Pacemaker Depolarization in Mammalian Sinoatrial Node Cells

Tamotsu Mitsuiye, Yasuko Shinagawa, Akinori Noma

From the Department of Physiology, Faculty of Medicine, Kyoto University, Kyoto, Japan.

Correspondence to Akinori Noma, Department of Physiology, Faculty of Medicine, Kyoto University, Sakyo-Ku, Yoshida-Konoe, Kyoto 606-8501, Japan. E-mail noma{at}card.med.kyoto-u.ac.jp

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 (I_st). 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 Ca²⁺ channels both in unitary conductance and gating kinetics. Because I_st 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 I_st for generation of intrinsic cardiac automaticity was suggested. (Circ Res. 2000;87:88-91.)

Key Words: cardiac pacemaker • sinoatrial node • sustained inward current

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