ß1-Subunit of the calcium-sensitive potassium channel modulates the pulmonary vascular smooth muscle cell response to hypoxia

Elizabeth A. Barnes, Lori Lee, Shayna L. Barnes, Robert Brenner, Cristina M. Alvira, David N. Cornfield

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Accessory subunits associated with the calcium-sensitive potassium channel (BKCa), a major determinant of vascular tone, confer functional and anatomical diversity. The ß1 subunit increases Ca2+ and voltagesensitivity of the BKCa channel and is expressed exclusively in smooth muscle cells. Evidence supporting the physiological significance of the ß1 subunit includes the observations that murine models with deletion of the ß1 subunit are hypertensive and that humans with a gain-of-function ß1 mutation are at a decreased risk of diastolic hypertension. However, whether the ß1 subunit of the BKCa channel contributes to the low tone that characterizes the normal pulmonary circulation or modulates the pulmonary vascular response to hypoxia remains unknown. To determine the role of the BKCa channel ß1 subunit in the regulation of pulmonary vascular tone and the response to acute and chronic hypoxia, mice with deletion of the Kcnmb1 gene that encodes for the ß1 subunit (Kcnmb1-/-) were placed in chronic hypoxia (10% O2) for 21–24 days. In normoxia, right ventricular systolic pressure (RVSP) did not differ between Kcnmb1+/+ (con-trols) and Kcnmb1-/- mice. After exposure to either acute or chronic hypoxia, RVSP was higher in Kcnmb1-/- mice compared with Kcnmb1+/+ mice, without increased vascular remodeling. ß1 subunit expression was predominantly confined to pulmonary artery smooth muscle cells (PASMCs) from vessels < 150 μm. Peripheral PASMCs contracted collagen gels irrespective of ß1 expression. Focal adhesion expression and Rho kinase activity were greater in Kcnmb1-/- compared with Kcnmb1+/+ PASMCs. Compromised PASMC ß1 function may contribute to the heightened microvascular vasoconstriction that characterizes pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)L265-L275
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume315
Issue number2
DOIs
StatePublished - Aug 2018

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Keywords

  • Focal adhesions
  • MaxiK channel
  • Microvasculature
  • Pulmonary artery smooth muscle cells
  • Rho kinase

ASJC Scopus subject areas

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

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