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- W2321360102 abstract "Background: Voltage-dependent L-type Ca2+ channel (VDCCL) of vascular smooth muscle is facilitated by mechanical stimuli, which is thought to contribute to the myogenic contraction of resistant arteries. However, the molecular mechanisms underlying the VDCCL activation is controversial.Aim and Methods: We examined the hypothesis that the remodeling of caveolae and its downstream signaling contributes to the facilitation of VDCCL by mechanical stretch in rat mesenteric arterial smooth muscle cells using patch-clamp technique and biochemical analysis.Results: Hypotonic membrane stretch (HMS) reversibly increased VDCCL current. HMS also induced caveolar reorganization as well as the phosphorylation of caveolin-1. Methyl-b cyclodextrin (MβCD) also reorganized caveolae and increased VDCCL. Subsequent application of HMS did not further increase the VDCCL, indicating stretch and cyclodextrin increased VDCCL via common pathway. Both the HMS and MβCD phosphorylated c-Jun N-terminal protein kinase (JNK), of which inhibition prevented the HMS-induced VDCCL facilitation. Caveolin-1 knockdown with siRNA blocked HMS-induced JNK phosphorylation and VDCCL activation. High KCl (70 mM)-induced [Ca2+]i increase was markedly facilitated by HMS and this facilitation was significantly attenuated by caveolin-1 knockdown. Finally actin cytoskeletal disruption with cytochalasin-D blocked HMS-induced phosphorylations of caveolin-1 and JNK and facilitation of VDCCL and [Ca2+]i increase.Conclusion: These results indicate hypotonic stretch activates VDCCL by actin-cytoskeleton-dependent caveolar reorganization. Phosphorylation of caveolin-1 seems to be closely associated with the caveolar remodeling. Activation of JNK is induced by caveolar remodeling and transduces this signal to VDCCL activation. These results define a novel function for caveolae, cavelolin-1 and JNK in stretch-induced activation of VDCCL." @default.
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- W2321360102 date "2015-01-01" @default.
- W2321360102 modified "2023-09-28" @default.
- W2321360102 title "Remodeling of Caveolae Mediates Stretch-Induced Increase of L-Type Calcium Current in Rat Mesenteric Artery" @default.
- W2321360102 doi "https://doi.org/10.1016/j.bpj.2014.11.3087" @default.
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