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

Abstract

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 4 s). 4. The depolarization in the centre of the node was abolished by block of the hyperpolarizationactivated current (if) by Cs+ or zatebradine (UL-FS 49). It could, therefore, result from the activation of if 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.

Decreased Vagal Control Over Heart Rate in Rats With Right-Sided Congestive Heart Failure-Downregulation of Neuronal Nitric Oxide Synthase-

“…9 Western blotting showed a single band at 160 kDa in atrial tissue samples from both control and CHF rats (Fig 5C). This corresponds to the nNOS band in rat cerebellar tissues.…”

“…In our previous studies on rabbit SA node tissue preparations we have shown that the intervening acceleration is abolished or minimized in the presence of blockers of If, and the secondary slowing is reduced by cutting the atrial muscle away from the SA node. 9,18 The elimination of the intervening acceleration in the CHF rats could be reconciled by an attenuation of the NO-cGMP system, as NO can directly stimulate the spontaneous beating of SA node pacemaker cells though an activation of If. 19 The elimination of the secondary slowing in the CHF rats might be the result of diminished function of vagal nerves in the atrial muscle surrounding the SA node.…”

“…Composition of the solution was as follows (in mmol/L): NaCl 120.3, KCl 4.0, CaCl2 1.2, MgSO4 1.3, NaH2PO4 1.2, NaHCO3 25.2, glucose 5.6 (pH 7.4). Spontaneous activity of the preparation was monitored by a pair of modified bipolar electrodes (MBE) 9 placed at the periphery of the SA node. A pair of silver wire electrodes (0.5 mm in diameter) with an interpolar distance of 3 mm was placed on the endocardial surface of the preparation.…”

“…One electrode was located on the atrial muscle and the other on the center of the SA node. 9 A train of 10-50 pulses (100 s at 200 Hz) was applied by field stimulation during spontaneous activity of the SA node. The intensity of the stimuli was adjusted to a level (~20 V) of subthreshold for excitation of the SA node and atrial muscle, but sufficient to stimulate postganglionic nerve terminals.…”

Creation of a Biopacemaker: Lessons from the Sinoatrial Node

“…The proteins responsible for the tetramers, Kir3.1 (KCNJ3) and Kir3.4 (KCNJ5), were indeed identified by immunofluorescence in rat SA node . Apart from the direct and short lasting hyperpolarizing effect of I K,ACh on the SA node, the increase in I K,ACh in surrounding atrial muscle leads to a longer lasting effect on the SA node by electrotonic interaction (Kodama et al, 1996).…”