BK Channel β1 Subunit Regulation of Calcium Handling and Constriction in Tracheal Smooth Muscle

The large conductance, calcium-activated (BK-type) potassium channels are regulators of voltage-dependent calcium entry in many cell types. The BK channel accessory β1 subunit promotes channel activation in smooth muscle and is required for proper tone in the vasculature and bladder. However, although BK channels have also been implicated in airway smooth muscle function, their regulation by the β1 subunit had not been investigated. We have investigated the role of the β1 subunit in tracheal smooth muscle by utilizing the gene targeted mice for the β1 subunit gene. Mice containing the β1 knockout allele had significantly reduced BK channel activity in excised tracheal smooth muscle patches, and had reduced spontaneous BK currents in whole tracheal smooth muscle cells. The consequence of the β1 knockout was an increase in resting calcium levels, and an increase in the sustained component of calcium influx following cholinergic signaling. Tracheal constriction studies demonstrate that the β1 knockout have the relatively same level of constriction as compared to BK channel block with paxilline, indicating that BK channels contribute little to airway relaxation in the absence of the β1 subunit. Utilizing nifedipine, we found that the increase constriction caused by the β1 knockout could be accounted for by an increased recruitment of L-type voltagedependent calcium channels. These results indicate that the β1 subunit is required in airway smooth muscle for BK channels to control voltage-dependent calcium influx during rest and following cholinergic signaling.