| First Author | Li M | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 5 | Pages | 3668-77 |
| PubMed ID | 23255603 | Mgi Jnum | J:195657 |
| Mgi Id | MGI:5484980 | Doi | 10.1074/jbc.M112.426585 |
| Citation | Li M, et al. (2013) The beta1-subunit of the MaxiK channel associates with the thromboxane A2 receptor and reduces thromboxane A2 functional effects. J Biol Chem 288(5):3668-77 |
| abstractText | The large conductance voltage- and Ca(2+)-activated K(+) channel (MaxiK, BK(Ca), BK) is composed of four pore-forming alpha-subunits and can be associated with regulatory beta-subunits. One of the functional roles of MaxiK is to regulate vascular tone. We recently found that the MaxiK channel from coronary smooth muscle is trans-inhibited by activation of the vasoconstricting thromboxane A(2) prostanoid receptor (TP), a mechanism supported by MaxiK alpha-subunit (MaxiKalpha)-TP physical interaction. Here, we examined the role of the MaxiK beta1-subunit in TP-MaxiK association. We found that the beta1-subunit can by itself interact with TP and that this association can occur independently of MaxiKalpha. Subcellular localization analysis revealed that beta1 and TP are closely associated at the cell periphery. The molecular mechanism of beta1-TP interaction involves predominantly the beta1 extracellular loop. As reported previously, TP activation by the thromboxane A(2) analog U46619 caused inhibition of MaxiKalpha macroscopic conductance or fractional open probability (FP(o)) as a function of voltage. However, the positive shift of the FP(o) versus voltage curve by U46619 relative to the control was less prominent when beta1 was coexpressed with TP and MaxiKalpha proteins (20 +/- 6 mV, n = 7) than in cells expressing TP and MaxiKalpha alone (51 +/- 7 mV, n = 7). Finally, beta1 gene ablation reduced the EC(50) of the U46619 agonist in mediating aortic contraction from 18 +/- 1 nm (n = 12) to 9 +/- 1 nm (n = 12). The results indicate that the beta1-subunit can form a tripartite complex with TP and MaxiKalpha, has the ability to associate with each protein independently, and diminishes U46619-induced MaxiK channel trans-inhibition as well as vasoconstriction. |
