Functional and molecular consequences of ionizing irradiation on large conductance Ca2+-activated K+ channels in rat aortic smooth muscle cells.

Aims: The goal of this study was to evaluate the influence of gamma-irradiation on Ca(2+)-activated K(+) channel (BK(Ca)) function and expression in rat thoracic aorta.

Main Methods: Aortic cells or tissues were studied by the measurement of force versus [Ca(2+)](i), patch-clamp technique, and RT-PCR.

Key Findings: Stimulation of smooth muscle cells with depolarizing voltage steps showed expression of outward K(+) currents. Paxilline, an inhibitor of BK(Ca) channels, decreased outward K(+) current density. Outward currents in smooth muscle cells obtained from irradiated animals 9 and 30 days following radiation exposure demonstrated a significant decrease in K(+) current density. Paxilline decreased K(+) current in cells obtained 9 days, but was without effect 30 days after irradiation suggesting the absence of BK(Ca) channels. Aortic tissue from irradiated animals showed progressively enhanced contractile responses to phenylephrine in the post-irradiation period of 9 and 30 days. The concomitant Ca(2+) transients were significantly smaller, as compared to tissues from control animals, 9 days following irradiation but were increased above control levels 30 days following irradiation. Irradiation produced a decrease in BK(Ca) alpha- and beta(1)-subunit mRNA levels in aortic smooth muscle cells suggesting that the vasorelaxant effect of these channels may be diminished.

Significance: These results suggest that the enhanced contractility of vascular tissue from animals exposed to radiation may result from an increase in myofilament Ca(2+) sensitivity in the early post-irradiation period and a decrease in BK(Ca) channel expression in the late post-irradiation period.