Phasic effects of vagal stimulation on pacemaker activity of the isolated sinus node of the young cat.

Abstract

SUMMARYWe studied the functional interactions between the sinoatrial (SA) nodal pacemaker and the vagus nerve in isolated right atrium-vagus nerve preparations of the kitten. Brief trains of stimuli applied to the vagus nerve scanning the spontaneous pacemaker cycle induce a brief hyperpolarization of the membrane of cells in the pacemaker region. Aa a result of this hyperpolarization, there occur phasic changes in pacemaker cycle length that depend on the timing, amplitude, and duration of the hyperpolarization and, also, on the relationship between the duration of the hyperpolarization and the pacemaker cycle length. If the duration of the hyperpolarization is long relative to the duration of the spontaneous cycle, the next discharge can be delayed but not accelerated, no matter when during the cycle vagal stimuli are applied. If the duration of the hyperpolarization is briefer than the spontaneous cycle and the vagal input is presented early in the cycle, a postinhibitory rebound accelerates the next discharge. These effects of the vagal burst on the pacemaker cycle can be described by an inhibitory curve consisting of several components: a latent period of about 200 msec, a phase of major prolongation of the first and sometimes the second pacemaker cycle, a phase of relative or actual acceleration, and a final phase of lesser deceleration lasting several seconds. These effects can be approximated closely in a sucrose gap preparation of the sinus node by brief hyperpolarizing current pulses spanning the spontaneous pacemaker cycle in the test compartment. Ore Re* 45: 595-607, 1979 THE EFFECTS of parasympathetic discharges on the sinoatrial (SA) node are characterized by a brief latency and brief duration; accordingly, the magnitude of the cardiac response to brief bursts of vagal stimuli bears a phasic relationship to the timing of the nerve impulses in the cardiac cycle (Brown and Eccles, 1934;Stade and Weiss, 1956;Levy et al., 1970;Dong and Reitz, 1970;Eckberg, 1976). Particularly at slow heart rates, discrete bursts of discharges in efferent cardiac vagal fibers may be related to the arterial pressure pulses, resulting in complex frequency-dependent interactions between the cardiac pacemaker and the vagal activity (Jewett, 1964;Katona et al., 1970;Iriuchijima and Kumada, 1963).Recent studies (Levy et al., 1969;Reid, 1969; have demonstrated that periodically repeated vagal stimuli can entrain the SA nodal pacemaker so that its cycle length assumes a fixed ratio to that of the stimulus interval. Spontaneous pacemaker activity in isolated strands of Purkinje tissue mounted in a sucrose-gap preparation also can be entrained by the electrotonic effects of depolarizing and hyperpolarizing current pulses (Jalife and Moe, 1976). Hyperpolarizing pulses induced early in the pacemaker cycle accelerate, and pulses of similar magnitude initiated late in the cycle delay the subsequent discharge. Because vagal stimuli have been shown to cause hyperpolarization in cells of the SA node and of the atrium, we have undert...

A mathematical model of the effects of acetylcholine pulses on sinoatrial pacemaker activity.

“…To terminate the pulse, the opening rate coefficient, « u , was set to zero. This technique produced a membrane hyperpolarization similar in shape and time course to that seen experimentally (Jalife and Moe, 1979;Jalife et al, 1980). With different versions of the computer programs, three simulation protocols were used: (1) the application of a single, brief ACh pulse, (2) the repetitive application of brief ACh pulses at fixed ACh inter-pulse intervals, and (3) the repetitive application of brief ACh pulses at fixed sinus response-ACh pulse intervals (i.e., fixed coupling).…”

“…Brief efferent vagal bursts, such as those induced reflexly by the systolic pulse wave (Iriuchijima and Kumada, 1963) or respiratory activity (Anrep et al, 1936), can either abbreviate or prolong the sinus pacemaker cycle (Levy et al, , 1972Spear et al, 1979;Stuesse et al, 1981;. The magnitude and direction of the effect depend upon the intrinsic pacemaker period (cycle length), the intensity and duration of the vagal stimulus, and, most important, the time of occurrence of the vagal pulse during the pacemaker cycle Jalife and Moe, 1979). Previous studies from our laboratory have investigated the nature of dynamic vagus-SA node interactions for singly and repetitively applied vagal pulses.…”

The Role of Muscarinic K+Channels in the Negative Chronotropic Effect of a Muscarinic Agonist

“…3A). In the baroreflex, the efferent cardiac vagal activity occurs more or less fixed to the cardiac cycle (Jewett, 1964;Katona et al, 1970), and the effectiveness of vagal activity on the sinus automaticity is strongly dependent on the relationship between the pacemaker cycle and the duration, amplitude, and timing of the hyperpolarizing effect of vagal impulses (Jalife and Moe, 1979). K ACh channels possess a sufficiently fast response time to ACh to mediate such a phasic effect of vagal activity (Breitwieser and Szabo, 1988;Inomata et al, 1989), at least in part due to the direct coupling of the channels with G proteins and the regulator of G protein signaling proteins (Doupnik et al, 1997;Yamada et al, 1998).…”

Effect of clonidine on cardiac baroreflex delay in humans and rats

“…[Sympathetic actions may be ignored because they are too slow to mediate reflex changes with a 0-to 2-beat delay (9,21,34,55)]. It is well established that there is a fixed latency imposed by vagal neuroeffector transmission at the cardiac pacemaker (6,21,23). This is due to the time taken between the occupation by acetylcholine of postjunctional M 2 muscarinc receptors and the changes in pacemaker cell currents mediated by G protein-coupled signaling pathways (12).…”