On the mechanism of spontaneous impulse generation in the pacemaker of the heart.

Rhythmic activity in Purkinje fibers of sheep and in fibers of the rabbit sinus can be produced or enhanced when a constant depolarizing current is applied. When extracellular calcium is reduced successively, the required current strength is less, and eventually spontaneous beating occurs. These effects are believed due to an increase in steady-state sodium conductance. A significant hyperpolarization occurs in fibers of the rabbit sinus bathed in a sodium-free medium, suggesting an appreciable sodium conductance of the "resting" membrane. During diastole, there occurs a voltage-dependent and, to a smaller extent, time-dependent reduction in potassium conductance, and a pacemaker potential occurs as a result of a large resting sodium conductance. It is postulated that the mechanism underlying the spontaneous heart beat is a high resting sodium current in pacemaker tissue which acts as the generator of the heart beat when, after a regenerative repolarization, the decrease in potassium conductance during diastole reestablishes the condition of threshold.