| First Author | Barnes EA | Year | 2018 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 315 |
| Issue | 2 | Pages | L265-L275 |
| PubMed ID | 29644895 | Mgi Jnum | J:264251 |
| Mgi Id | MGI:6194667 | Doi | 10.1152/ajplung.00060.2018 |
| Citation | Barnes EA, et al. (2018) beta1-Subunit of the calcium-sensitive potassium channel modulates the pulmonary vascular smooth muscle cell response to hypoxia. Am J Physiol Lung Cell Mol Physiol 315(2):L265-L275 |
| abstractText | Accessory subunits associated with the calcium-sensitive potassium channel (BKCa), a major determinant of vascular tone, confer functional and anatomical diversity. The beta1 subunit increases Ca(2+) and voltagesensitivity of the BKCa channel and is expressed exclusively in smooth muscle cells. Evidence supporting the physiological significance of the beta1 subunit includes the observations that murine models with deletion of the beta1 subunit are hypertensive and that humans with a gain-of-function beta1 mutation are at a decreased risk of diastolic hypertension. However, whether the beta1 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 beta1 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 beta1 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(+/+) (controls) 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. beta1 subunit expression was predominantly confined to pulmonary artery smooth muscle cells (PASMCs) from vessels </= 150 microm. Peripheral PASMCs contracted collagen gels irrespective of beta1 expression. Focal adhesion expression and Rho kinase activity were greater in Kcnmb1(-/-) compared with Kcnmb1(+/+) PASMCs. Compromised PASMC beta1 function may contribute to the heightened microvascular vasoconstriction that characterizes pulmonary hypertension. |
