title: Role of individual ionic current systems in the SA node hypothesized by a model study.
abstract: This paper discusses the development of a cardiac sinoatrial (SA) node pacemaker model. The model successfully reconstructs the experimental action potentials at various concentrations of external Ca2+ and K+. Increasing the amplitude of L-type Ca2+ current (I(CaL)) prolongs the duration of the action potential and thereby slightly decreases the spontaneous rate. On the other hand, a negative voltage shift of I(CaL) gating by a few mV markedly increases the spontaneous rate. When the amplitude of sustained inward current (I(st)) is increased, the spontaneous rate is increased irrespective of the I(CaL) amplitude. Increasing [Ca2+](o) shortens the action potential and increases the spontaneous rate. When the spontaneous activity is stopped by decreasing I(CaL) amplitude, the resting potential is nearly constant (-35 mV) over 1-15 mM [K+](o) as observed in the experiment. This is because the conductance of the inward background non-selective cation current balances with the outward [K+](o)-dependent K+ conductance. The unique role of individual voltage- and time-dependent ion channels is clearly demonstrated and distinguished from that of the background current by calculating an instantaneous zero current potential ("lead potential") during the course of the spontaneous activity.
authors.affiliation: Department of Physiology and Biophysics, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sarai
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kuratomi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.forename: Akinori
authors.initials: A
authors.lastname: Noma
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology; D003198:Computer Simulation; D003971:Diastole / Q000502:physiology; D006168:Guinea Pigs; D007473:Ion Channels / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology; D007477:Ions / Q000032:analysis / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D012849:Sinoatrial Node / Q000166:cytology / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D007473:Ion Channels; D007477:Ions; D011188:Potassium; D002118:Calcium