ИСТИНА

Introduction: The TASK-1 channels (K2P family member) conduct background K+ current in arterial smooth muscle and, consequently, can stabilize the membrane potential and suppress vasoconstriction. Anticontractile influence of several K+-channels (Kir and Kv7) may strongly decrease with maturation, this question is still open regarding K2P channels. We hypothesized that TASK‐1 channel contribution to arterial vascular tone and blood pressure is higher in the early postnatal period than in adulthood. Methods: We studied 10‐ to 15‐day‐old (“young”) and 2‐ to 3‐monthold (“adult”) male rats performing digital PCR (dPCR) (using endothelium‐intact saphenous arteries), isometric myography, sharp microelectrode technique, quantitative PCR (qPCR) and Western blotting (using endothelium‐denuded saphenous arteries), and arterial pressure measurements in the carotid artery under urethane anaesthesia. Results: We found mRNA of Kcnk1–Kcnk7, Kcnk12, and Kcnk13 genes to be expressed in rat saphenous artery, and Kcnk3 (TASK‐1) and Kcnk6 (TWIK‐2) were most abundant in both age groups. The TASK‐1 channel blocker AVE1231 (1 μmol/L) prominently depolarized arterial smooth muscle and increased basal tone level and contractile responses to methoxamine of arteries from young rats but had almost no effect in adult rats. The level of TASK‐1 mRNA and protein expression was higher in arteries from young compared with adult rats. Importantly, intravenous administration of AVE1231 (4 mg/kg) had no effect on mean arterial pressure in adult rats but prominently raised it in young rats. Conclusion: We showed that TASK‐1 channels are important for negative feedback regulation of vasocontraction in young but not adult rats. Such influence of TASK‐1 channels most likely contributes to low blood pressure level at perinatal age. Supported by RSF (grant N19-15-00210) and DAAD (Short-Term Grants, 2018). We thank Sanofi for the gift of AVE1231.