Effects of timing of vagal stimulation on the sinoatrial nodal cell discharge.

The effects of vagal stimulation on the activity of the isolated rabbit sino-atrial (SA) node preparation were studied using electrophysiological techniques. Brief stimulus trains, which were subthreshold for the myocardial cells, were applied in order to release acetylcholine (ACh) from the nerve terminals. Transmembrane potentials were recorded from the follower cells located at the exit site near the pacemaker region. As the time from peak of the action potential to delivery of the vagal stimuli was progressively increased, the sinus cycle length first became progressively prolonged, and then was rapidly reduced to the control value. In order to resolve the underlying mechanisms for the phase-dependency, the effects of vagal stimulation were examined in a quiescent SA node preparation. When one stimulus was applied, membrane hyperpolarization began after a latency of 70 msec and developed slowly, reaching its peak value after about 270 msec, and its total time course was about 630 msec. Oscillatory potentials were observed after the recovery of the vagal-induced hyperpolarization; such oscillations were not observed in atrial myocardial cells. It is concluded that the slow-onset long-lasting response of the SA node cell membrane to ACh may play a role in the phase-dependent effect of vagal stimulation.