First Author | Noda S | Year | 2020 |
Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 318 |
Issue | 2 | Pages | L366-L375 |
PubMed ID | 31800260 | Mgi Jnum | J:287869 |
Mgi Id | MGI:6390236 | Doi | 10.1152/ajplung.00331.2019 |
Citation | Noda S, et al. (2020) Roles of LRRC26 as an auxiliary gamma1-subunit of large-conductance Ca(2+)-activated K(+) channels in bronchial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 318(2):L366-L375 |
abstractText | In visceral smooth muscle cells (SMCs), the large-conductance Ca(2+)-activated K(+) (BK) channel is one of the key elements underlying a negative feedback mechanism that is essential for the regulation of intracellular Ca(2+) concentration. Although leucine-rich repeat-containing (LRRC) proteins have been identified as novel auxiliary gamma-subunits of the BK channel (BKgamma) in several cell types, its physiological roles in SMCs are unclear. The BKgamma expression patterns in selected SM tissues were examined using real-time PCR analyses and Western blotting. The functional contribution of BKgamma1 to BK channel activity was examined by whole cell patch-clamp in SMCs and heterologous expression systems. BKgamma1 expression in mouse bronchial SMCs (mBSMCs) was higher than in other several SMC types. Coimmunoprecipitation and total internal reflection fluorescence imaging analyses revealed molecular interaction between BKalpha and BKgamma1 in mBSMCs. Under voltage-clamp, steady-state activation of BK channel currents at pCa 8.0 in mBSMCs occurred in a voltage range comparable to that of reconstituted BKalpha/BKgamma1 complex. However, this range was much more negative than in mouse aortic SMCs (mASMCs) or in HEK293 cells expressing BKalpha alone and beta-subunit (BKbeta1). Mallotoxin, a selective activator of BK channel that lacks BKgamma1, dose-dependently activated BK currents in mASMCs but not in mBSMCs. The abundant expression of BKgamma1 in mBSMCs extensively facilitates BK channel activity to keep the resting membrane potential at negative values and prevents contraction under physiological conditions. |