The Study into the Role of Pannexin 1 in the Regulation of Contractile Activity of Longitudinal Smooth Muscle Layer in the Mouse Portal Vein

Pannexin 1 is a protein capable of forming channels for the release of ATP from animal cells. In small arteries, it regulates the contraction of smooth muscle cells due to a functional connection with α_1D-adrenoceptors. Veins differ from arteries in structure and mechanisms of regulation of contraction, but the functions of pannexin in the venous bed have been poorly studied. The purpose of this study was to investigate the involvement of pannexin 1 in regulating the rhythmic contractile activity of the longitudinal smooth muscle layer in the mouse portal vein. The contractions of longitudinal vein specimens obtained from mice with global knockout of pannexin 1 gene and from С57Bl/6J mice (wild type) were studied in isometric mode. Venous specimens from both groups of mice demonstrated spontaneous rhythmic activity but the frequency of contractions in pannexin 1 knockout mice was higher than in wild-type mice. The α₁-adrenoceptor agonists phenylephrine and methoxamine stimulated venous contractions. In the knockout group, the effect of phenylephrine, which has a higher affinity for α_1D-adrenoceptors, was lower, while the effect of methoxamine did not differ between groups. Evoking an increase in the frequency of vein contractions, exogenous ATP also demonstrated a less pronounced effect in pannexin 1 knockout mice compared to wild-type mice. While the change in the frequency of vein contractions induced by phenylephrine and ATP (but not methoxamine) inversely correlated with the baseline frequency of contractions in wild-type mice, such dependence was not observed in knockout mice. In the presence of apyrase, which degrades extracellular ATP, the effect of phenylephrine on venous contraction frequency became less pronounced in wild-type mice but remained unchanged in knockout mice. Thus, pannexin does not directly participate in the generation of myogenic rhythmic activity in the mouse portal vein but may regulate it. The results suggest that, in the longitudinal smooth muscle layer of the mouse portal vein, pannexin 1 channels serve as the main pathway for ATP secretion and they are functionally associated with α_1D-adrenоreceptors.