Regional differences in the response of the isolated sino-atrial node of the rabbit to vagal stimulation.

1. The effects of brief postganglionic vagal nerve stimulation on electrical activity in different regions of the rabbit sino-atrial node and surrounding atrial muscle were recorded. 2. At the centre of the node (the leading pacemaker site), the brief stimulation resulted in a large hyperpolarization followed by a depolarization and a shortening of the action potential. All effects were short lasting (time to 90% recovery of membrane potential, 0.8 s). 3. At other sites within the node and in the surrounding atrial muscle, although there was still a substantial action potential shortening, the hyperpolarization was smaller and the depolarization was small or absent. All effects were longer lasting (time to 90% recovery in atrial muscle, 11.4s). 4. The depolarization in the centre of the node was abolished by block of the hyperpolarization-activated current (i(f)) by Cs+ or zatebradine (UL-FS 49). It could, therefore, result from the activation of i(f) during the preceding hyperpolarization. 5. Block of acetylcholinesterase by eserine greatly slowed recovery from vagal stimulation at all sites, demonstrating that recovery is dependent on acetylcholinesterase. The longer lasting effects of vagal stimulation in atrial muscle, therefore, result from lower acetylcholinesterase activity. 6. Vagal stimulation resulted in a short lasting initial slowing of spontaneous action potentials followed by a long-lasting secondary slowing. Whereas the initial slowing coincided with the effects of vagal stimulation on the centre of the node, the secondary slowing coincided with the slower effects of vagal stimulation on the surrounding atrial muscle. The secondary slowing was reduced by 68 +/- 11% (n = 5) by cutting the atrial muscle away from the node. 7. It is concluded that the short-lasting initial slowing of spontaneous action potentials is the direct effect of vagal stimulation on the centre of the sino atrial node, whereas the secondary slowing is the result of the longer lasting effects of vagal stimulation on the surrounding atrial muscle and the electrotonic suppression of the node by the muscle.