Phase resetting properties of cardiac pacemaker cells

Aggregates of heart cells from chicken embryos beat spontaneously. We used intracellular microelectrodes to record the periodic behavior of the membrane potential that triggers the contractions. Every 5-12 beats, a short current pulse was applied at various points in the cycle to study the phase-dependent resetting of the rhythm. Pulses stronger than 2.5 nA caused the final rhythm to be reset to almost the same point in the cycle regardless of the phase at which the pulse was applied (type zero resetting). Pulses of less than or equal to 1 nA only caused a slight change of the phase. Increasing current intensities to between 1 and 2.5 nA gave rise to an increasing steepness in a small part of the phase-response curve. The observation of type zero resetting implies the existence of a critical stimulation that might annihilate the rhythm. Although we did find a phase at which more or less random responses occurred, the longest pause in the rhythm was 758 ms, 2.4 times the spontaneous interval. This suggests that the resting membrane potential was unstable, at least against the internal noise of the system. The conclusions are discussed in terms of the concepts of classical cardiac electrophysiology.