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PMID:14592808
| Citation |
Wang, YX, Zheng, YM, Mei, QB, Wang, QS, Collier, ML, Fleischer, S, Xin, HB and Kotlikoff, MI (2004) FKBP12.6 and cADPR regulation of Ca2+ release in smooth muscle cells. Am. J. Physiol., Cell Physiol. 286:C538-46 |
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| Abstract |
Intracellular Ca2+ release through ryanodine receptors (RyRs) plays important roles in smooth muscle excitation-contraction coupling, but the underlying regulatory mechanisms are poorly understood. Here we show that FK506 binding protein of 12.6 kDa (FKBP12.6) associates with and regulates type 2 RyRs (RyR2) in tracheal smooth muscle. FKBP12.6 binds to RyR2 but not other RyR or inositol 1,4,5-trisphosphate receptors, and FKBP12, known to bind to and modulate skeletal RyRs, does not associate with RyR2. When dialyzed into tracheal myocytes, cyclic ADP-ribose (cADPR) alters spontaneous Ca2+ release at lower concentrations and produces macroscopic Ca2+ release at higher concentrations; neurotransmitter-evoked Ca2+ release is also augmented by cADPR. These actions are mediated through FKBP12.6 because they are inhibited by molar excess of recombinant FKBP12.6 and are not observed in myocytes from FKBP12.6-knockout mice. We also report that force development in FKBP12.6-null mice, observed as a decrease in the concentration/tension relationship of isolated trachealis segments, is impaired. Taken together, these findings point to an important role of the FKBP12.6/RyR2 complex in stochastic (spontaneous) and receptor-mediated Ca2+ release in smooth muscle. |
| Links |
PubMed Online version:10.1152/ajpcell.00106.2003 |
| Keywords |
Acetylcholine/pharmacology; Animals; Calcium/metabolism; Chlorides/metabolism; Cyclic ADP-Ribose/metabolism; Horses; Immunosuppressive Agents/pharmacology; Membrane Potentials/drug effects; Membrane Potentials/physiology; Mice; Mice, Knockout; Myocytes, Smooth Muscle/physiology; RNA, Messenger/analysis; Ryanodine Receptor Calcium Release Channel/metabolism; Sarcoplasmic Reticulum/metabolism; Tacrolimus/pharmacology; Tacrolimus Binding Proteins/genetics; Tacrolimus Binding Proteins/metabolism; Trachea/cytology |
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Significance
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