In rat sinoatrial node, NAD+ (10 μM) reduced the rate of spontaneous action potentials, duration of action potentials, and the velocity of slow diastolic depolarization, but the rate of action potential front propagation increases. In passed rabbit Purkinje fi bers, NAD+ (10 μM) reduced the duration of action potentials. Under conditions of spontaneous activity of Purkinje fi bers, NAD+ reduced the fi ring rate and the rate of slow diastolic depolarization. The effects of extracellular NAD+ on bioelectric activity of the pacemaker (sinoatrial node) and conduction system of the heart (Purkinje fi bers) are probably related to activation of P1 and P2 purinoceptors.

This study is aimed to the investigation of the nicotinamide adenine dinucleotide (NAD+) effects and mechanisms of action in a heart. NAD+ (mcM) induces multiphase alternation of contractile activity of isolated rat heart: short positive inotropic action is followed by a negative inotropic phase. NAD+ (1-100 mcM) induces decreasing of action potential duration (APD) in rat atrial myocardium (from 45 +/- 0.82 ms in control experiments to 39 +/- 1.05 (n = 8) and 32 +/- 2 (n = 8) during application of 10 and 100 mcM of NAD+, respectively). Significant APD increase (from 45 +/- 0.82 ms to 74 +/- 1.89 (n = 8) ms) was observed during washing out of NAD+ (100 mcM). ATP or adenosine was unable to increase APD both during application or washing out. NAD+ induced APD decrease was not suppressed by P1-antagonist theophylline. P1-purinoreceptor and metabolite independent direct action of NAD+ in rat heart is suggested. Activation of P2X or P2Y receptors, cyclic ADP-ribose accumulation in cardiomyocytes is proposed as a main mechanism of NAD(+)-induced effects in the heart.

We studied the effect of selective activation of muscarinic M3 receptors on electrical activity in the isolated preparation of rat ventricular myocardium as well as contractile activity of the left ventricle of Langendorff-perfused isolated heart. Application of muscarinic agonist pilocarpine (10−5 M) against the background of selective blockade of subtype 2 muscarinic receptors with methoctramine (10−7 M) markedly shortened the duration of action potentials in the isolated ventricular myocardium and reduced the amplitude and maximum rates of left-ventricular pressure rise and decay in the isolated heart paced at a fixed rate. All these effects were significantly suppressed by selective M3 receptor blocker 4-DAMP (10−8 M), which attested to the involvement of M3 muscarinic receptors.

We studied the effects of carbon monoxide and sodium hydrosulfide, hydrogen sulfide donor, on contractile activity of the left ventricle in Langendorf-perfused isolated rat heart. Carbon monoxide 5×10−5 M significantly accelerated sinus rhythm and left-ventricular pressure wave growth and decay. To the contrary, negative inotropic and chronotropic effects were observed at higher concentrations of carbon monoxide (10−4, 3×10−4 M). Sodium hydrosulfide (10−4-4×10−4 M) decreased all the parameters of left-ventricular contractive activity and reduced contraction rate. Carbon monoxide and hydrogen sulfide, which together with nitrogen oxide are qualified as a new class of gaseous signal compounds, may substantially modulate pumping function of the heart.

The regulation of body-wall muscle contraction in the ascidian Styela rustica was studied. Acetylcholine (ACh, 1–10 μM) induced a significant contraction of isolated muscle strips. The ACh-induced contractile response was potentiated and prolonged in the presence of proserine (15 μM), which confirms acetylcholinesterase activity in the S. rustica body-wall muscle. Atropine (1–100 μM, M-cholinoreceptor blocker) did not prevent the ACh-induced contractile response, while d-tubocurarine (1–100 μM, N-cholinoreceptor blocker) progressively reduced muscle contraction induced by 10 μM ACh. Thus, neuromuscular transmission in the S. rustica body-wall muscle is mediated by nicotinic-like ACh-receptors. Procaine reduced ACh-induced (10 μM) muscle contraction. As well, our experiments showed spontaneous rhythmic contractile activity in isolated muscle strips of S. rustica. Atropine, d-tubocurarine, procaine, and proserine did not alter rhythmic activity. Myogenic automaticity is suggested as a possible cause of the rhythmic contraction of the ascidian body-wall muscle.

Changes of the activation sequence in the rabbit sinoatrial node under the influence of low temperature and I(f) selective blocker ivabradine have been studied using the optical mapping technique. Both factors caused a shift of the pacemaker within the sinoatrial node region. These results are compared with the data obtained recently in the investigation of pacemaker shift under the influence of cholinergic and adrenergic factors. Possible mechanisms of the pacemaker shift are discussed. The suppression of electric activity in the central part of the sinoatrial node during the action of acetylcholine, which is called cholinergic inexcitability, may be considered as one of the mechanisms of the pacemaker shift. It is shown that the main cause of cholinergic inexcitability is the activation of potassium acetylcholine-dependent current I(KACh).

Changes of electric activity induced by acetylcholine were studied in atrial myocardium of fishes (cod and carp) and reptilians (lizard and grass-snake). Standart microelectrode technique and novel method of optical mapping were used in the study. Acetylcholine (1-50 microM) provoked decrease of the action potential amplitude down to full inhibition of electrical activity in wide regions of atrium of cod and carp. We define this phenomenon as cholinergic inexcitability. In other regions excitation persisted even during action of 500 microM acetylcholine. In atria of lizard and grass-snake acetylcholine caused shortening of action potential without changes in it's amplitude. Local cholinergic inexcitability, shown in the atrial myocardium of fishes, is quite similar to the phenomenon, that was described earlier in the atria of frogs. It presents the heart of fish as an interesting model for study of mechanisms of cholinergic atrial arrhythmias initiation.

We used high resolution optical mapping for the study of activation sequence in a rabbit sinoatrial node in normal state and during artificial stimulation as well as changes of excitation chronotopography under cholinergic influences. In the norm excitation originates in central region of sinoatrial node. During acetylcholine action (10, 50, 100 M) and activation of intramural parasympathetic nerves suppression of electrical activity in the zone of initial pacemaker localization occurs. Suppression of activation is associated with pacemaker migration within sinoatrial node and lowering of the rate of generation of excitation. Termination of cholinergic influences has been followed by restoration of initial chronotopography of excitation. During artificial stimulation of sinoatrial node nonexitable (refractory) area has been formed in the region of initial localization of the natural pacemaker.