Effects of Extracellular Diadenosine Tetraphosphate on Action Potentials in the Atrial and Ventricular Myocardium of the Rat Heart during Early Postnatal Ontogenesis

Diadenosine tetraphosphate (AP4A) belongs to a wide group of naturally derived endogenous purine compounds that have recently been considered as new neurotransmitters in the autonomic nervous system. It has been shown that AP4A induces inhibitory effects and modulates adrenergic control in the heart of adult mammals. Nevertheless, the physiological significance of AP4A in early postnatal development, when sympathetic innervation remains yet immature, has not been investigated. The aim of the present study was to elucidate the effects of AP4A on the heart bioelectrical activity in early postnatal ontogenesis. Action potentials (AP) were recorded using the standard microelectrode technique in multicellular isolated right atrial (RA), left atrial (LA), and ventricle (RV) preparations from male Wistar rats at postnatal days 1, 14, and 21 and from 60-day animals that were considered as adults. The application of AP4A caused significant reduction of AP duration in atrial (RA and LA) preparations from rats of all ages. Also, AP4A caused significant AP shortening in RV preparations from rats of various ages; however, the effect was more pronounced in 21-day-old and adult rats. AP4A failed to alter automaticity of RA preparations from the rats at postnatal days 1, 14, and 21 and weakly decreased spontaneous rhythm in RA preparations from the adult rats. The effect of AP4A was partially abolished by P2-receptor blocker PPADS in LA preparations from both 21-dayold and adult rats, while it failed to suppress AP4A-caused AP shortening in preparations from 1- and 14-dayold animals. Thus, extracellular AP4A causes shortening of AP both in the atrial and ventricular myocardium in the rats of early postnatal ontogenesis and in adults. The effect of AP4A depends on age only for ventricular myocardium where it may be attributed with growing contribution of diadenosine polyphosphates to the control of myocardium inotropy.