Влияние блокады пейсмекерных токов на сердце крыс при формировании адренергической иннервации

Abstract

Hyperpolarization-activated currents (If) contribute to the generation of spontaneous electrical activity in the heart. If are modulated by the cAMP level, sympathetic, and parasympathetic parts of the autonomic nervous system. The innervation development is an important factor in the formation of the ionic current orchestra in the cardiomyocytes. The age of 6 weeks in rats poses a particular interest, because at that point the heart rate is at its slowest, and the adrenergic innervation completes its development. The aim of thist study was to investigate the role of If current in the myocardial function regulation at one of the stages of sympathetic heart innervation development. The analysis of the results revealed that in the experiments on Langendorf-isolated heart the application of If blocker ZD 7288 in 10-9-10-5 M concentrations to rats of this age led to a decrease in the heart rate. ZD 7288 in 10-8-10-5 M concentrations reduced the left ventricular pressure and the coronary flow of the isolated heart in 6-week old rats. The perfusion of the isolated heart with If blocker in 10-9 M concentration increased the left ventricular pressure, but did not affect the coronary flow. In the studies of the atrial cardiomyocyte electrical activity, ZD7288 (10-7-10-5M) increased the action potential duration at the 50% and 90% repolarization level, and reduced the action potential generation frequency. Together, these results show that the If blockade affects the heart rate, heart contraction force, and coronary flow of the isolated heart of 6-week old rats. Apparently, the heart at the stage of completion of the adrenergic innervation development has a higher density of these currents than in adult rats, which manifests in a more pronounced response to the If blockade. The changes in the heart contraction force can be attributed to the changes in the repolarization phase duration of the working cardiomyocytes.