The time- and voltage-dependent gating of ionic channels plays a primary role in the automaticity of membrane potential changes. The experimental evidence described so far indicates that the following gating mechanisms underlie the slow diastolic depolarization. The delayed rectifier K+ channels are activated during the preceding action potential and are deactivated by the negative potential during diastole. The deactivation of K+ channels results in the time-dependent depolarization of the membrane, provided that the amplitude of the background inward current is of significant amplitude. The inactivation of the L-type Ca2+ channels is gradually removed during the early diastolic period and this channel gating results in a time-dependent increase in the inward current. Because of its sustained nature, Ist also contributes to the net inward current. The negative membrane potential near the maximum diastolic potential activates If. Finally, the later phase of diastole depolarization activates the L-type Ca2+ channel, triggering the maximum rate of rise of the action potential. These time- and voltage-dependent changes in membrane conductance occur in the presence of a significant background conductance. Channel gating driving membrane depolarization during diastole. Deactivation of IK Removal of inactivation of ICa,L Activation of Ist Activation of If Activation of ICa,L Activation of ICa,T Background conductances Ib,Na IK,ACh INa/K INa/Ca IK,ATP The central question is the relative amplitudes of these current components. These would be quantitatively estimated over the entire range of the diastolic depolarization by incorpolating the experimentally-derived characteristics of each current system into a mathematical model of the pacemaker action potential. To date various types of SA node models have been proposed. (Yanagihara, Noma, & Irisawa, 1980; Noble, & Noble, 1984; Wilders, Jongsma, & Van Ginneken, 1991; Demir et al., 1994). Our model (Sarai et al., 2003) successfully reconstructs the experimental action potentials at various concentrations of external Ca2+ and K+. Increasing the amplitude of L-type Ca2+ current (ICaL) prolongs the duration of the action potential and thereby slightly decreases the spontaneous rate. On the other hand, a negative voltage shift of ICaL gating by a few mV markedly increases the spontaneous rate. When the amplitude of sustained inward current (Ist) is increased, the spontaneous rate is increased irrespective of the ICaL amplitude. Increasing [Ca2+]o shortens the action potential and increases the spontaneous rate. When the spontaneous activity is stopped by decreasing ICaL amplitude, the resting potential is around –35 mV over 1-15 mM [K+]o because of the presence of the background non-selective cation current. 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 equilibrium potential during the course of the spontaneous activity.