At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are called "funny" currents and abbreviated as "If". These depolarizing currents cause the membrane potential to begin to spontaneously depolarize, thereby initiating Phase 4. As the membrane potential reaches about -50 mV, another type of channel opens. This channel is called transient or T-type Ca++ channel. As Ca++ enters the cell through these channels down its electrochemical gradient, the inward directed Ca++ currents further depolarize the cell. When the membrane depolarizes to about -40 mV, a second type of Ca++ channel opens. These are the so-called long-lasting, or L-type Ca++ channels. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually between -40 and -30 mV). It should be noted that a hyperpolarized state is necessary for pacemaker channels to become activated. Without the membrane voltage becoming very negative at the end of phase 3, pacemaker channels remain inactivated, which suppresses pacemaker currents and decreases the slope of phase 4. This is one reason why cellular hypoxia, which depolarizes the cell and alters phase 3 hyperpolarization, leads to a reduction in pacemaker rate (i.e., produces bradycardia). During Phase 4 there is also a slow decline in the outward movement of K+ as the K+ channels responsible for Phase 3 continue to close. This fall in K+ conductance (gK+) contributes to the depolarizing pacemaker potential.
