BK channel β1-subunit regulation of calcium handling and constriction in tracheal smooth muscle

Iurii Semenov, Bin Wang, Jeremiah T. Herlihy, Robert Brenner

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The large-conductance, Ca2+-activated K+ (BK) channels are regulators of voltage-dependent Ca2+ 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 has not been investigated. Utilizing the gene-targeted mice for the β1-subunit gene, we have investigated the role of the β1-subunit in tracheal smooth muscle. In mice with the β1-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 β1-subunit resulted in an increase in resting Ca2+ levels and an increase in the sustained component of Ca2+ influx after cholinergic signaling. Tracheal constriction studies demonstrate that the level of constriction is the same with knockout of the β1- subunit and BK channel block with paxillin, indicating that BK channels contribute little to airway relaxation in the absence of the β1-subunit. Utilizing nifedipine, we found that the increased constriction caused by knockout of the β1-subunit could be accounted for by an increased recruitment of L-type voltage-dependent Ca 2+ channels. These results indicate that the β1- subunit is required in airway smooth muscle for control of voltage-dependent Ca2+ influx during rest and after cholinergic signaling in BK channels.

Original languageEnglish (US)
Pages (from-to)L802-L810
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume291
Issue number4
DOIs
StatePublished - Oct 9 2006

Keywords

  • Airway
  • Gene-targeted mice
  • Knockout mice

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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