This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitsuiye, T. Articles by Noma, A. Search for Related Content PubMed PubMed Citation Articles by Mitsuiye, T. Articles by Noma, A. Related Collections Electrophysiology Pacemaker Cell signalling/signal transduction

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

MiniReview

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

This article has been cited by other articles:

				M. E. Mangoni and J. Nargeot Genesis and Regulation of the Heart Automaticity Physiol Rev, July 1, 2008; 88(3): 919 - 982. [Abstract] [Full Text] [PDF]

				J. Liu, H. Dobrzynski, J. Yanni, M. R. Boyett, and M. Lei Organisation of the mouse sinoatrial node: structure and expression of HCN channels Cardiovasc Res, March 1, 2007; 73(4): 729 - 738. [Abstract] [Full Text] [PDF]

				D. M. Bers The Beat Goes On: Diastolic Noise That Just Won't Quit Circ. Res., October 27, 2006; 99(9): 921 - 923. [Full Text] [PDF]

				J. Stieber, K. Wieland, G. Stockl, A. Ludwig, and F. Hofmann Bradycardic and Proarrhythmic Properties of Sinus Node Inhibitors Mol. Pharmacol., April 1, 2006; 69(4): 1328 - 1337. [Abstract] [Full Text] [PDF]

				Y. Kurata, I. Hisatome, H. Matsuda, and T. Shibamoto Dynamical Mechanisms of Pacemaker Generation in IK1-Downregulated Human Ventricular Myocytes: Insights from Bifurcation Analyses of a Mathematical Model Biophys. J., October 1, 2005; 89(4): 2865 - 2887. [Abstract] [Full Text] [PDF]

				M. S. Wolin and S. A. Gupte Novel Roles for Nox Oxidases in Cardiac Arrhythmia and Oxidized Glutathione Export in Endothelial Function Circ. Res., September 30, 2005; 97(7): 612 - 614. [Full Text] [PDF]

				M. Lei, C. Goddard, J. Liu, A.-L. Leoni, A. Royer, S. S.-M. Fung, G. Xiao, A. Ma, H. Zhang, F. Charpentier, et al. Sinus node dysfunction following targeted disruption of the murine cardiac sodium channel gene Scn5a J. Physiol., September 1, 2005; 567(2): 387 - 400. [Abstract] [Full Text] [PDF]

				T. Krogh-Madsen, P. Schaffer, A. D. Skriver, L. K. Taylor, B. Pelzmann, B. Koidl, and M. R. Guevara An ionic model for rhythmic activity in small clusters of embryonic chick ventricular cells Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H398 - H413. [Abstract] [Full Text] [PDF]

				D. J. Huelsing, K. W. Spitzer, and A. E. Pollard Spontaneous activity induced in rabbit Purkinje myocytes during coupling to a depolarized model cell Cardiovasc Res, September 1, 2003; 59(3): 620 - 627. [Abstract] [Full Text] [PDF]

				Y. Kurata, I. Hisatome, S. Imanishi, and T. Shibamoto Dynamical description of sinoatrial node pacemaking: improved mathematical model for primary pacemaker cell Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H2074 - H2101. [Abstract] [Full Text] [PDF]

				G. Schram, M. Pourrier, P. Melnyk, and S. Nattel Differential Distribution of Cardiac Ion Channel Expression as a Basis for Regional Specialization in Electrical Function Circ. Res., May 17, 2002; 90(9): 939 - 950. [Abstract] [Full Text] [PDF]

				D. M. Bers Calcium and Cardiac Rhythms: Physiological and Pathophysiological Circ. Res., January 11, 2002; 90(1): 14 - 17. [Full Text] [PDF]

				M. E. Mangoni and J. Nargeot Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells Cardiovasc Res, October 1, 2001; 52(1): 51 - 64. [Abstract] [Full Text] [PDF]