ИСТИНА

Introduction. The TASK-1 channels conduct background K+-current in arterial smooth muscle and, consequently, can stabilize the membrane potential and suppress vasoconstriction. Noteworthy, anticontractile influence of several K+-channels (Kir and Kv7) decreases with maturation. However, the developmental alterations of TASK-1 vasomotor role have not been studied yet. We hypothesized that the impact of TASK-1 channels on peripheral vascular tone and systemic arterial pressure (AP) decreases during postnatal development. Materials and Methods. Isometric force and membrane potential were recorded simultaneously in endothelium-denuded saphenous arteries using wire myography and the sharp microelectrode technique. mRNA expression level was determined in endothelium-denuded arterial samples by qPCR. AP was recorded in the carotid artery under urethane anesthesia. Results. In arteries from young (10-15-days) male rats, TASK-1 blocker AVE1231 (1 µM, kindly provided by Sanofi) induced strong basal depolarization (23 mV) and tone development (35% of max active force) and potentiated the effects of α1-adrenoceptor agonist methoxamine on membrane potential and active force. In contrast, in arteries of adult (2-3-months) male rats, AVE1231 caused only moderate depolarization (10 mV), not associated with either tone development or changes in methoxamine-induced contractions. mRNA content of TASK-1 pore-forming subunit was significantly higher in samples of young rats compared to adults. Importantly, the increase of AP by AVE1231 (4 mg/kg, i.v.) was stronger in young than in adult rats. Conclusions. The anticontractile role of TASK-1 channels in rat saphenous artery and its influence on AP level is particularly strong in early postnatal period, in contrast to mature organism.