Effects of current flow on pacemaker activity of the isolated kitten sinoatrial node

The dynamic behavior of the cardiac pacemaker in response to single or to periodically repeated perturbations was studied using kitten sinoatrial (SA) nodal strips mounted in a sucrose gap. Sustained stepwise applications of current across the gap produce lasting variations in pacemaker cycle length that depend on current magnitude and polarity, but not on the phase of the pacemaker period at the time of the input. Brief current pulses, whether hyperpolarizing or depolarizing, may abbreviate or prolong the immediately affected cycle depending on their timing. These changes result in phase shifts of the subsequent discharges, but they do not alter the pacemaker period permanently. The phasic effects of brief current pulses can be described by a phase response curve (PRC), which is a plot of the phase shift as a function of the position of the stimulus in the pacemaker cycle. PRCs were constructed for inputs of different polarity and several strengths and durations. The behavior of the sinus nodal pacemaker when interacting with period perturbing inputs, such as vagal stimulation or electrotonic depolarization, can be predicted on the basis of the phase response curve.