Effect of transmural vagal stimulation on electrotonic current spread in the rabbit sinoatrial node.

OBJECTIVE: The effect of vagal stimulation on the decay of electrotonic potential caused by intracellular current injection and on input resistance was measured in the sinoatrial node of isolated rabbit right atria. METHODS: Studies were performed on New Zealand White rabbits weighing approximately 2-3 kg. Vagal stimulation was achieved by transmural stimulation of intramural nerve fibres in the presence of propranolol. A K+ perfused suction electrode was used to inject hyperpolarising current pulses; input resistance was measured by means of a double barrel microelectrode. RESULTS: Vagal stimulation which caused a 14-20% increase of cycle length diminished electronic potential significantly by a decrease of membrane resistance. The input resistance of the sinoatrial node was not affected. Space constant values calculated by using either a one or a two dimensional model of electrotonic current spread were decreased on average by 13% and 14% respectively. CONCLUSIONS: The results from this study show that vagal stimulation which gave rise to a moderate negative chronotropic effect and marked changes in action potential configuration of nodal fibres affects the electrotonic interaction within the sinoatrial node. This may have consequences for the electrical activity and synchronisation of the sinoatrial nodal fibres.

Phase dependency of electrotonic spread of hyperpolarizing current pulses in the rabbit sinoatrial node.

Electrotonic current spread in the SA node of the rabbit was measured by means of hyperpolarizing current pulses (1 to 10 microA, 60 ms), which were injected intracellularly through a K(+)-perfused suction electrode. The pulses were applied at the beginning, middle or end of the diastolic depolarization phase. The resulting membrane potential change of nodal fibers was measured with microelectrodes. Space constants were calculated by fitting single exponential curves to the data. The input resistance (Rin) of fibers at different sites in the SA node was measured by means of a double barrel microelectrode (current pulses 5.5 to 11 nA, 60 ms) to detect a change in the internal resistance during the diastolic depolarization phase. During diastole the average electrotonic potential increased by 30% (P less than 0.001), the increase of the space constant ranged from 9 to 183% (P less than 0.05). Rin however, did not change during diastole. It is concluded that the electrotonic spread increased phase dependently, due to an increase of membrane resistance; the internal resistance was not phase dependent.

Anisotropy of electrotonus in the sinoatrial node of the rabbit heart.

In fibers of the sinoatrial node of isolated right atria of rabbits the decay of the electrotonic potential caused by intracellular current injection was measured in two directions: parallel to the crista terminalis and perpendicular to it. A K+-perfused extracellular suction electrode was used to apply current pulses (10(-5) A, 60 ms) to fibers located in the primary center of the SA node every fourth cardiac cycle at a fixed moment during diastole. The decay of the electrotonic spread was measured in a series of impalements on a straight line from the current source. Space constants were calculated by fitting single exponential curves to the data. Considerable regional differences in space constant values were found in either direction. Parallel to the crista terminalis the mean value was 529 +/- 446 microns (S.D., n = 7), perpendicular to it 306 +/- 295 microns (n = 12); the difference was not significant (P less than 0.2). However, a significant anisotropy (P less than 0.05) of the electrotonic spread was found when measurements were taken from small areas of the node. Large abrupt changes in the electrotonic potential within 200 microns were observed in the center of the node. These data indicate a non-uniformity of electrotonic spread in this part of the SA node.

Alinidine as a model of the mode of action of specific bradycardic agents on SA node activity.

Three different bradycardic agents, alinidine, AQ-A39 and UL-FS49 increase the intrinsic cycle length of the isolated SA node preparation of the rabbit. This increase is mainly caused by a decrease in rate of diastolic depolarization. One of these agents, alinidine, was used to study the underlying ionic mechanism of the decrease in the diastolic depolarization rate in isolated cells and small cell clusters of the rabbit SA node. In these preparations alinidine slowed down the rate of spontaneous activity at higher concentrations (80 microM). At lower concentrations (10 microM) the decrease in rate of spontaneous activity was variable, but injection of a hyperpolarizing current slowed the spontaneous rate more in the presence of alinidine, indicating an increase in membrane resistance. In voltage clamp experiments we found that the main effect of alinidine was a block of the hyperpolarization activated current if. The block was potential dependent and was maximal in the potential range in which diastolic depolarization occurs. These results are discussed in relation to previous findings of others.

Electrophysiological effects of alinidine (ST 567) on sinoatrial node fibres in the rabbit heart.

In a study of the electrophysiological effects of alinidine a concentration of 0.7-14.3 mumol X litre-1 decreased the rate of diastolic depolarisation and prolonged especially the terminal part of the action potential in the rabbit sinoatrial node. It did not induce pacemaker shifts since the effects were not restricted to the primary pacemaker or the central nodal area but were evident in the more peripheral nodal region. The substitution of chlorine ions by other anions did not prevent the decrease in the rate of diastolic depolarisation due to alinidine but did prevent the effect on the action potential duration. The decreased chronotropic action of alinidine in low chlorine Tyrode solution was, however, caused by a shift of pacemaker dominance towards an atrial pacemaker. This pacemaker shift concealed the response of the primary pacemaker to alinidine in low chlorine Tyrode. Blockade of the pacemaker current of if by caesium prevented neither the alinidine effect on the diastolic depolarisation completely nor its effect on the action potential duration, but blockade of if probably was one of the determinants of the action of alinidine. It cannot be excluded that alinidine interferes with still another current than if. Alinidine decreased the chronotropic responses to adrenaline and to acetylcholine and also prevented pacemaker shifts due to these substances.

Electrophysiological effects of alinidine on nodal and atrial fibers in the guinea-pig heart.

The effect of alinidine on transmembrane electrical activity of nodal and atrial fibers was studied in the isolated right auricle of the guinea-pig. Alinidine was applied in concentrations between 0.72 and 28.5 X 10(-5) M. In nodal fibers the main effect was a dose-dependent decrease in rate of diastolic depolarization and a delayed repolarization of especially the terminal part of the action potential. In both fiber types alinidine causes a marked delay of the terminal part of repolarization; the increase of the duration of the action potential was related to the alinidine concentration over the whole concentration range used. In addition the amplitude of the action potential and the maximal diastolic potential are increased dose dependently up to a concentration of 2.8 x 10(-5) M. Application of higher concentrations does not increase these parameters. In nodal fibers diastolic depolarization is already depressed considerably at a relatively low concentration. This is particularly so in fibers that normally have a high rate of diastolic depolarization, i.e., the dominant pacemaker fibers. A shifting of the pacemaker seems only to occur at high concentrations (11.4 X 10(-5) M or higher). The strong negative chronotropic effect of alinidine can be attributed to both the depression of diastolic depolarization and the increase in duration of the action potential. At low concentrations the increase of the maximum diastolic potential can also contribute to the slowing of the heart rate.