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1 Subunit Regulation of Calcium Handling and Constriction in Tracheal Smooth Muscle
1 Physiology, UT Health Science Center San Antonio, San Antonio, Texas, United States
* To whom correspondence should be addressed. E-mail: brennerr{at}uthscsa.edu.
The large conductance, calcium-activated (BK-type) potassium channels are regulators of voltage-dependent calcium entry in many cell types. The BK channel accessory 
1 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 1 subunit had not been investigated. We have investigated the role of the 1 subunit in tracheal smooth muscle by utilizing the gene targeted mice for the 1 subunit gene. Mice containing the 1 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 1 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 1 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 1 subunit. Utilizing nifedipine, we found that the increase constriction caused by the 1 knockout could be accounted for by an increased recruitment of L-type voltage-dependent calcium channels. These results indicate that the 1 subunit is required in airway smooth muscle for BK channels to control voltage-dependent calcium influx during rest and following cholinergic signaling.
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