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

Abstract

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) α and β subunits and BK(Ca) currents are present in the rat DA, as well as whether the BK(Ca) channels are involved in O₂-induced ductal constriction. BK(Ca) α and β 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) α mRNAs decreased with advancing development. β1 was the dominant β subunit in the DA, and the amount of β1 mRNAs was greatest in the mature DA. Immunofluorescence staining showed that the majority of BK(Ca) α and β1 proteins were colocated with alpha smooth muscle actin (α-SMA) in the tunica media of the DA in all age groups. The protein expression of the α subunit was greatest in the mature DA, while the expression of the β1 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 O₂ sensitivity and no response to BK(Ca) inhibitor (paxilline) or activator (NS1619). The 21D ductus rings developed significant constriction induced by O₂. 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 O₂-induced ductal constriction. Activation of BK(Ca) channels led to vasodilatation in the preconstricted DA induced by O₂, possibly suggesting a way to maintain the patency of DA after birth.