The role of the large-conductance voltage-dependent and calcium-activated potassium (BK(Ca)) channels in the regulation of rat ductus arteriosus tone.

摘要

The role of large-conductance voltage-dependent and calcium-activated potassium (BK(Ca)) channels in the regulation of ductus arteriosus (DA) tone is not clear. This study aimed to examine whether BK(Ca) alpha and beta subunits and BK(Ca) currents are present in the rat DA, as well as whether the BK(Ca) channels are involved in O-induced ductal constriction. BK(Ca) alpha and beta subunit transcripts (mRNAs) were detected in the DA from premature (19D) and mature (21D) rat fetuses and full-term neonates (NB) by quantitative real-time PCR. The amount of BK(Ca) alpha mRNAs decreased with advancing development. beta1 was the dominant beta subunit in the DA, and the amount of beta1 mRNAs was greatest in the mature DA. Immunofluorescence staining showed that the majority of BK(Ca) alpha and beta1 proteins were colocated with alpha smooth muscle actin (alpha-SMA) in the tunica media of the DA in all age groups. The protein expression of the alpha subunit was greatest in the mature DA, while the expression of the beta1 subunit did not differ among all three groups. The 19D and 21D ductus tensions were recorded under various conditions by myograph. The 19D ductus rings exhibited poor O sensitivity and no response to BK(Ca) inhibitor (paxilline) or activator (NS1619). The 21D ductus rings developed significant constriction induced by O. Paxilline did not increase the 21D DA tension under either hypoxic or oxygenated conditions. NS1619 dilated the 21D DA only under oxygenated conditions. The recorded BK(Ca) currents were greatest in the 21D DA smooth muscle cells (SMCs) upon using a whole-cell patch clamp. Our study indicated that BK(Ca) channels exist in the DA but are not involved in O-induced ductal constriction. Activation of BK(Ca) channels led to vasodilatation in the preconstricted DA induced by O, possibly suggesting a way to maintain the patency of DA after birth.