Abstract
Membrane transporters and their functional contribution in vasculature change during early postnatal development. Here we tested the hypothesis that the contribution of Cl− channels to arterial contraction declines during early postnatal development and this decline is associated with the trophic sympathetic influence. Endothelium‐denuded saphenous arteries from 1- to 2-week-old and 2- to 3-month-old male rats were used. Arterial contraction was assessed in the isometric myograph, in some experiments combined with measurements of membrane potential. mRNA and protein levels were determined by qPCR and Western blot. Sympathectomy was performed by treatment with guanethidine from the first postnatal day until 8–9-week age. Cl− substitution in the solution as well as Cl−-channel blockers (MONNA, DIDS) had larger suppressive effect on the methoxamine-induced arterial contraction and methoxamine-induced depolarization of smooth muscle cells in 1- to 2-week-old compared to 2- to 3-month-old rats. Vasculature of younger group demonstrated elevated expression levels of TMEM16A and bestrophin 3. Chronic sympathectomy increased Cl− contribution to arterial contraction in 2-month-old rats that was associated with an increased TMEM16A expression level. Our study demonstrates that contribution of Cl− channels to agonist-induced arterial contraction and depolarization decreases during postnatal development. This postnatal decline is associated with sympathetic nerves development.
Highlights
Membrane transporters and their functional contribution in vasculature change during early postnatal development
We have prevoiusly demonstrated that the contribution of C l− to arterial contraction decreases during postnatal maturation of v asculature[15]
In the arteries from 2- to 3-month-old rats as well as from 1- to 2-week-old rats the responses to α1-adrenoceptor agonist methoxamine were significantly reduced in C l− free physiological salt solution (PSS) in comparison with normal PSS (Fig. 1)
Summary
Membrane transporters and their functional contribution in vasculature change during early postnatal development. Chronic sympathectomy increased Cl− contribution to arterial contraction in 2-month-old rats that was associated with an increased TMEM16A expression level. Our study demonstrates that contribution of Cl− channels to agonist-induced arterial contraction and depolarization decreases during postnatal development. This postnatal decline is associated with sympathetic nerves development. Agonist-induced smooth muscle cell activation (e.g. by noradrenaline via α1-adrenoceptors) causes Ca2+ release from intracellular stores, C a2+ influx through channels in cell membrane and sensitization of contractile apparatus to C a2+. All these mechanisms lead to the contraction of smooth muscle cells. The role of C l− channels in these changes and the mechanisms behind it remain to be elucidated
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