Depolarization automaticity was modeled on the papillary muscle from the guinea pig heart. Phosphoenolpyruvate (0.1 mM) 2-fold decreased the high-frequency calcium-dependent automaticity, but only weakly affected frequency of action potentials, whose upstroke was formed by fast sodium current or had a mixed nature. Phosphoenolpyruvate shifted the diastolic potential toward negative values, which depended on the amplitude of depolarization step. These effects developed 10-15 min after application of the preparation.Key Words: phosphoenolpyruvate; depolarization automaticity; action potential Glycolysis intermediates produced pronounced antiischemic and antiarrhythmic effect in animals with acute coronary occlusion and reperfusion [ 1,8,9,11 ]. Taking into consideration the involvement of cell metabolism in the genesis of cardiac arrhythmias [5,12], the antiarrhythmic effect of these substances can be explained by prolongation of the glycolytic energy production in cardiomyocytes [3,6,7]. However, participation of common electrophysiological mechanisms [13] in the antiarrhythmic effect of glycolysis intermediates was not yet assessed.Our aim was to study the effect of phosphoenolpyruvate (PEP) on electrical activity of isolated myocardial ventricles.
MATERIALS AND METHODSThe study was carried out on guinea pigs weighing 250-350 g. The papillary muscles were isolated from the right ventricle under nembutal narcosis. The muscle were mounted in a chamber (2 ml) and perfused with oxygenated Tyrode solution (35~ pH 7.4) containing (in mM): 130 NaCI, 2.7 KC1, 2.0 CaCl2, 1.0 MgC12, 10 glucose, and 5 HEPES-NaOH.Membrane potential was measured with 10-20-M.Q glass microelectrodes. The signal and its first derivative were recorded with an automatic differentiator Department of Pharmacology, Mordovian State University, Saransk (Micromed). The duration of action potentials (AP) corresponding to 50 and 90% repolarization was measured. The preparations were stimulated with the trains of rectangular pulses applied via bipolar silver electrodes. The duration and frequency of pulses in the train were 1 msec and 1 Hz, respectively.The depolarization automaticity was modeled according to [2]. The rectangular direct current impulses were applied at a rate of 1 Hz via silver-chloride electrodes and an agar salt bridge from an ESU-2 electric stimulator (4.5-6.5 sec pulse duration), Membrane potential was recorded by the same method.In this study we used PEP tricyclohexylammonium salt (Sigma).
RESULTSInitially we evaluated the effect of PEP on some parameters of AP in persistently stimulated guinea pig papillary muscle. PEP (0.1 mM) produced a moderate, but significant decrease in AP duration by l 1 and 7% at the 50 and 90% repolarization level, respectively. These changes developed 3-5 min after application of PEP in Tyrode solution and reached a steady-state level after 10-15 min. The PEP-induced shortening of AP became reversible only after 30-60-min washout. The test substance did not change resting potential, AP amplitude, and maxim...