AND MOLECULAR BIOLOGY Study of the Preautomatic Pause under Exposure to Acetylcholine in True Pacemaker Cells of Rabbit Sinus Node Using Computer Simulation

Abstract

Preautomatic pause, which is required for the resto- Fig. 1, 20 nM acetylcholine caused the development of ration of automatism in pacemakers, plays a key role in such a pause. Long-term measurements of the potential heart functioning. In this work, we studied the effect of and intracellular concentrations of Na+, K+, and Ca2+ acetylcholine and the role of intracellular ion homeo- (Fig. 2) show that the concentrations of Na+ and K+ stasis on the occurrence of preautomatic pause in true gradually increased and decreased, respectively, upon pacemaker cells of rabbit sinus node. It is demonstrated stimulation, whereas the concentration of Ca2+ was rap-that, in the absence of acetylcholine, the pause is only idly adjusted to new steady-state values and practically 0.4 s, whereas in the presence of acetylcholine it may did not change until the end of stimulation (Fig. 2, t = last for tens seconds. The occurrence of the pause and 5–65 s). After the cessation of stimulation, the direction escape from it is determined by slow changes in intrac- of changes in the concentration of Na+ and K+ altered to ellular concentrations of Na+, K+, and Ca2+. Under- the opposite, and the fluctuations in the transmembrane threshold fluctuations in membrane potential of potential and intracellular Ca2+ were not observed ( t = increasing amplitude are the sign of automatism resto- 65–132 s). Note that the steady-state transmembrane ration. potential (approximately –40 mV) is close to the inac-Conditions of numerical experiments. The electrical activity of membranes of sinus-node cells and the effect of acetylcholine were studied in the model based on rabbit SN cells [1, 2]. When simulating the intracellular ion homeostasis, we took into account the changes in the concentration of Na, K