Аннотация:Potassium channels play an important role in the regulation of vascular tone. Their activation leads to hyperpolarization and relaxation of arterial smooth muscle. There are four types of potassium channels in arterial smooth muscle: voltage-dependent K+ channels (Kv, the most functionally relevant subtype in arterial smooth muscle is Kv7), Ca2+-activated K+ channels (BKCa), inward rectifier K+ channels (KIR), ATP-sensitive K+ channels (KATP). We hypothesized that the role of K+ channels in the regulation of vasocontractile responses changes during postnatal maturation.
Saphenous arteries were isolated from young (10-15-days old) and adult (2-3-month old) male rats, endothelium was denuded and arterial contractile responses were studied using wire myography. Blockers of KАТР (glibenclamide, 3 microМ), Kv7 (XE991, 3 microМ), ВKСа (iberiotoxin, 0.1 microМ) and KIR (BaCl2, 30 microM) channels were used in order to evaluate the role of different K+ channels in the regulation of basal tone and contractile responses to alpha1-adrenoceptor agonist methoxamine. mRNA expression levels were determined by qPCR.
KАТР blocker had no effect on basal tone and contractile responses to methoxamine in arteries in both groups. Blockade of Kv7 caused a significant increase of basal tone and contractile responses in young, but not adult rats; this was consistent with higher expression levels of Kv7.1 and Kv7.5 in arteries of young rat. The effects of BKCa blocker iberiotoxin were more prominent in arteries of adult animals. This was accompanied by higher expression level of beta-subunit of BKCa channel in their arteries, while the expression level of alpha-subunit was similar in saphenous arteries of young and adult rats. KIR blockade augmented contractile responses in both age groups, however the effects were more prominent in arteries of young animals.
In conclusion, our results show that in saphenous arteries (i) KATP channels have no impact on contractile responses to alpha1-adrenоceptor agonist in both age groups; (ii) the influence of Kv7 and KIR channels on the regulation of contractile responses decreases, while (iii) the contribution of BKCa increases during early postnatal ontogenesis.
This study was supported by the RFBR (grant № 16-04-01395-а).