BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle.
The large-conductance, Ca(2+)-activated K(+) (BK) channels are regulators of voltage-dependent Ca(2+) entry in many cell types. The BK channel accessory beta(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 beta(1)-subunit has not been investigated. Utilizing the gene-targeted mice for the beta(1)-subunit gene, we have investigated the role of the beta(1)-subunit in tracheal smooth muscle. In mice with the beta(1)-subunit-knockout allele, BK channel activity was significantly reduced in excised tracheal smooth muscle patches and spontaneous BK currents were reduced in whole tracheal smooth muscle cells. Knockout of the beta(1)-subunit resulted in an increase in resting Ca(2+) levels and an increase in the sustained component of Ca(2+) influx after cholinergic signaling. Tracheal constriction studies demonstrate that the level of constriction is the same with knockout of the beta(1)-subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the beta(1)-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the beta(1)-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca(2+) channels. These results indicate that the beta(1)-subunit is required in airway smooth muscle for control of voltage-dependent Ca(2+) influx during rest and after cholinergic signaling in BK channels.[1]References
- BK channel beta1-subunit regulation of calcium handling and constriction in tracheal smooth muscle. Semenov, I., Wang, B., Herlihy, J.T., Brenner, R. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
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