We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Caveolar remodeling is a critical mechanotransduction mechanism of the stretch-induced L-type Ca channel activation in vascular myocytes.
- Authors
Park, Sang; Shin, Kyung; Park, Hyun; Yoou, Soon-Kyu; Park, Jin-Yeon; Kang, Young-Sun; Sung, Dong; Kim, Jae; Park, Seung; Kim, BoKyung; Cho, Hana; Bae, Young
- Abstract
Activation of L-type voltage-dependent Ca channels (VDCC) by membrane stretch contributes to many biological responses such as myogenic contraction of arteries. However, mechanism for the stretch-induced VDCC activation is unclear. In this study, we examined the hypothesis that caveolar remodeling and its related signaling cascade contribute to the stretch-induced activation of VDCC in rat mesenteric arterial smooth muscle cells. The VDCC currents were recorded with nystatin-perforated or with conventional whole-cell patch-clamp technique. Hypotonic (~230 mOsm) swelling-induced membrane stretch reversibly increased the VDCC currents. Electron microscope and confocal imaging analysis revealed that both hypotonic swelling and cholesterol depletion by methyl-β-cychlodextrin (MβCD) similarly disrupted the caveolae structure and translocated caveolin-1 (Cav-1) from membrane to cytosolic space. Accordingly, MβCD also increased VDCC currents. Moreover, subsequent hypotonic swelling after MβCD treatment failed to increase the VDCC currents further. Western blotting experiments revealed that hypotonic swelling phosphorylated Cav-1 and JNK. Inhibitors of tyrosine kinases (genistein) and JNK (SP00125) prevented the swelling-induced facilitation of VDCC currents. Knockdown of Cav-1 by small interfering RNA blocked both the VDCC current facilitation by stretch and the related phosphorylation of JNK. Taken together, the results suggest that membrane stretch is transduced to the facilitation of VDCC currents via caveolar structure-dependent tyrosine phosphorylation of Cav-1 and subsequent activation of JNK in rat mesenteric arterial myocytes.
- Subjects
VOLTAGE-gated ion channels; MECHANOTRANSDUCTION (Cytology); ELECTRON microscopy; CAVEOLAE; CALCIUM channels; PROTEIN-tyrosine phosphatase; MYOBLASTS
- Publication
Pflügers Archiv: European Journal of Physiology, 2017, Vol 469, Issue 5/6, p829
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-017-1957-3