Effects of manganese chloride on the outward currents in frog atrial trabeculae.

The effects of MnCl2 on outward currents in frog atrial muscle were investigated under voltage-clamp conditions. MnCl2 (3 mmol/L), which completely abolished the slow inward current, produced a decrease in the outward background current (Ib) at potentials positive to -50 mV. The delayed outward current (Ix, time dependent) was not altered by Mn. "Isochronic activation curves" for Ix and decay of current tails at -40 mV remained unaffected after Mn. Effects on Ib probably reflect a decrease in IK1 related to the decrease in Ca influx as well as a reduction in the Na-Ca exchange current.

Effects of low pH on the action potential and contraction of normal and hypoxic papillary muscles.

The effects of low pH (6.5) on action potentials and contractions of rabbit papillary muscles were examined under aerobic and hypoxic conditions (pO2 = 65- 75 mmHg, 8.6-10.0 kPa). An acid medium reduced overshoot, Vmax of phase O and action potential duration, without changing the resting potential, under aerobic aerobic conditions. Maximum twitch tension was reduced and resting tension was increased by 40% and 6% respectively of control values. Upon returning to normal Tyrode, all parameters returned to control values. The effects of acidosis under hypoxic conditions were essentially the same as those described above; acidosis potentiated the effects of hypoxia. It is concluded that in the given experimental conditions, low pH potentiates the effects of hypoxia on electrical and contractile activity, although probably by different mechanisms. The effects of acid medium on the action potential could be well accounted for the a reduction in slow inward current and by an increase in outward background potassium current, probably in relation to an increase in internal free calcium concentration.

Influence of parasympathetic pathways on early post--infarction arrhythmias.

The close relation between heart rhythm disorders that follow acute myocardial infarction (MI) and autonomic nervous system activity has come into focus recently. In order to evaluate the influence of the parasympathetic outflow on the incidence and characteristics of the early arrhythmias that follow myocardial infarction, the authors developed an experimental model of MI in rabbits by acute occlusion of the left ventricular artery. They have found that after the acute experimental MI an early stage of rhythm disorders is developed in 60% of the animals. In a second group of animals submitted to vagotomy prior to coronary occlusion none of rabbits exhibited arrhythmias. A third experimental series was performed in animals pretreated with atropine before and during the coronary occlusion; in this group the incidence of arrhythmias was the same as in control animals. The haemodynamic data obtained from the animals pretreated with atropine were similar to those obtained in control animals. The influence of vagal afferent and efferent pathways and their role in the genesis of the early arrhythmias is discussed.

Action potential characteristics of rabbit papillary muscle.

The ionic components of the action potential (AP) in rabbit right papillary muscle (RRPM) were determined by simple methods such as changes in external concentrations of sodium and calcium ions and addition of MnCl2 ot the perfusion fluid. Two components (fast and slow) were clearly visible in the upstroke of AP in normal Tyrode solution. MnCl2 (5 mmol/l) eliminated the slow component which forms the overshoot (OS) leaving the fast one unaffected, indicating that the former was related to a slow inward current. Mn also drastically reduced AP duration without changing the slope of phase 3 of repolarization. Reduction of Na concentration to 90 mmol/l did not affect the peak voltage of the OS but shortened AP. This low-Na solution reduced both (Vmax)f and the amplitude of the fast component. Ca-free solution reduced OS and increased AP duration. In high-Ca Tyrode (7.2 mmol/l) OS was increased and AP shortened. The effects of MN were reversed in this solution. The results suggest that the upstroke of the RRPM action potential is determined by two different ionic currents: a fast Na current responsible for the fast component and a slow inward current carried mainly by Ca, this latter being responsible for the slow component in the upstroke and for the plateau phase. The existence of propagated, Ca-dependent slow responses was demonstrated. Emphasis is placed on the fact that the major determination of the repolarization process in this type of AP is probably the inactivation of the slow inward Ca current.

Effects of moderate hypoxia on action potential and contraction of rabbit ventricular muscle.

Experiments were performed on rabbit right ventricular strips in order to investigate the effects of moderate hypoxia on electrical and mechanical activities of this preparation. The results indicate that a slow inward current (Isi) is responsible for overshoot (OS) and the plateau phase of the action potential (AP). Hypoxia (pO2 = 65-70 mmHg; 8.66-10.0 kPa) induced a rapid shortening of AP and an increase in the phase-3 slope. It also markedly reduced twitch tension and time to peak tension, and increased resting tension. The resting potential (RP), OS and maximum rate of depolarization of phase O were not affected during 60 min of hypoxic perfusion. Isoproterenol under this condition had a positive inotropic effect and also increased AP duration (APD) measured at -60 mV, having a less pronounced effect on the plateau phase. MnCl2 in hypoxic conditions drastically reduced OS indicating that even in this condition, Isi was present. These results suggest that an increase in gK is responsible for the hypoxia-induced reduction in APD. This also partially explains the maintenance of RP during hypoxic incubation.

Electrophysiological effects of droperidol on sinoatrial nodal fibers.

The influence of 1 and 5 mg/l of droperidol on rabbit sinus node intracellular recordings was evaluated. At 1 mg/l the drug merely prolonged the spontaneous basic cycle by reducing phase 4 slope of the action potential. At the higher concentration, droperidol induced a more pronounced effect of these variables and after 20 min perfusion, it also decreased the upstroke velocity and the threshold potential. Further exposure continued to reduce spontaneous rate, until irregular failure of impulse initiation and subthreshold oscillations appeared. After 45 min exposure to droperidol, only subthreshold oscillations could be recorded. Isoproterenol (0.2 mg/l) rapidly restored normal action potentials, while acetylcholine (0.5 mg/l) caused an immediate arrest leaving a stable level of membrane potential. The activity of droperidol in 1 mg/l concentration could be dependent on a partial blockade of the sodium leakage current, while at higher concentrations of 5 mg/l the drug seems to provoke a total blockade of Na--Ca slow channels. Subthreshold oscillations could be explained by changes in K conductance together with a remanent of the sodium leakage current.

Effects of atrial premature stimulation on sinus node function in isolated rabbit atria.

The effects of premature atrial depolarizations (PADs) on the sinus node function were studied in isolated rabbit atria by using simultaneous intracellular recordings in the sinus node and adjacent regions. Late PADs (test cycle 85% or more of the basic cycle) did not capture the sinus node, blocking somewhere between this structure and the crista terminalis, inducing however a shortening of action potential, an increased rate of rise (Vmax) and amplitude of phase 0, and a variable depression of phase 4 depolarization on sinus node fibres. These effects were attributed to electrotonic interactions. Earlier PADs (test cycle 45--85% of the basic cycle) penetrated and captured the sinus node, changing its action potential shape, depending on the prematurity of the response. Two major effects were demonstrated: 1) a reduction in the maximum diastolic potential; 2) a linearly-related (p less than 0.001) decrease of the slope of phase 4 depolarization. These effects resulted in a depression of sinus node automaticity that was inversely-related to the test cycle length. Dominant pacemaker shifts within the sinus node were frequently observed with early as well as with late PADs resulting in a change of the basic cycle by as much as 90 msec. It is concluded that the use of the technique of premature atrial stimulation may not permit precise evaluation of sinoatrial conduction time.