"Fade" of hyperpolarizing responses to vagal stimulation at the sinoatrial and atrioventricular nodes of the rabbit heart.

Previous studies have suggested that maintained vagal stimulation or acetylcholine infusion results in a fade of responses in the sinoatrial node but not in the atrioventricular node, implying different muscarinic receptor subtypes in the two regions. We investigated this hypothesis in 23 isolated rabbit atrial preparations made quiescent by continuous superfusion with verapamil (1 microgram/ml). Transmembrane potentials were recorded simultaneously from cells in the sinoatrial pacemaker region and from the "N" region of the atrioventricular node. Postganglionic vagal stimulation was achieved by the application of trains of pulses (50-150 microseconds; 10-20 V; 200 Hz). Simultaneous application of long-lasting (1-10 sec) vagal trains produced hyperpolarizations which were nearly identical for both nodal regions. Maximal hyperpolarizations (approximately or equal to 24 mV for sinoatrial node; 26 mV for atrioventricular node) were reached about 500 msec after initiation of the vagal train. Thereafter, hyperpolarizations faded, following a biphasic time course, and thus displaying two different time constants, one fast (tau fast = 580 msec for sinoatrial node; 550 msec for atrioventricular node), and one slow (tau slow = 9.2 sec for both sinoatrial and atrioventricular nodes). Hyperpolarizations during brief (200-msec) but repetitive vagal trains also faded biphasically, but approached a steady state much more rapidly than responses to long-lasting trains. Recovery from hyperpolarization decay occurred rather slowly and was linear. Our results demonstrate that the membrane potential responses to vagal stimulation in the atrioventricular node are indistinguishable from those in the sinoatrial node, and suggest that similar muscarinic receptors are operative in both regions. These phenomena may play an important role in the response of the cardiac conducting system to direct or reflexly mediated vagal input.