| First Author | Huster M | Year | 2010 |
| Journal | FASEB J | Volume | 24 |
| Issue | 8 | Pages | 2651-9 |
| PubMed ID | 20371628 | Mgi Jnum | J:162339 |
| Mgi Id | MGI:4818727 | Doi | 10.1096/fj.09-149856 |
| Citation | Huster M, et al. (2010) A complex of CaV1.2/PKC is involved in muscarinic signaling in smooth muscle. FASEB J 24(8):2651-9 |
| abstractText | Here we present functional and biochemical evidence for a Ca(2+) channel (Ca(V)1.2) /protein kinase C (PKC) signaling complex being a key player in muscarinic regulation of urinary bladder smooth muscle. Muscarinic stimulation induced Ca(2+) signals and concomitant contractions in detrusor muscle from mice that were dependent on functional Ca(2+) channels. These signals were still present in muscles being depolarized by 85 mM extracellular K(+). Muscarinic-induced contractions were reduced by a PKC inhibitor [bisindolylmaleimide I (BIM-I)] and a phospholipase D (PLD) inhibitor (1-butanol). A phorbol ester (PDBu) enlarged muscarinic-induced Ca(2+) signals and contractions. The effects of BIM-I and PDBu were inhibited by isradipine and/or absent in muscles from Ca(V)1.2-deficient mice. Both carbachol and PDBu increased Ca(V)1.2 channel currents in isolated bladder myocytes. Blue native-PAGE electrophoresis revealed that Ca(V)1.2, PKC, and PLD are closely associated in muscles being previously stimulated by carbachol. Immunoprecipitation using anti-Ca(V)1.2 followed by Western blotting demonstrated that Ca(V)1.2 and PKC are coupled in stimulated muscles from wild-type mice. Autoradiography on immunoprecipitates showed that Ca(V)1.2 is a substrate for PKC-mediated phosphorylation. These findings suggest that a signaling complex consisting of Ca(V)1.2, PKC, and, probably, PLD controls muscarinic-mediated phasic contraction of urinary bladder smooth muscle.-Huster, M., Frei, E., Hofmann, F., Wegener, J. W. A complex of Ca(V)1.2/PKC is involved in muscarinic signaling in smooth muscle. |
