Stretch-induced Ca(2+) release via an IP(3)-insensitive Ca(2+) channel.
Various mechanical stimuli increase the intracellular Ca(2+) concentration ([Ca(2+)](i)) in vascular smooth muscle cells (VSMC). A part of the increase in [Ca(2+)](i) is due to the release of Ca(2+) from intracellular stores. We have investigated the effect of mechanical stimulation produced by cyclical stretch on the release of Ca(2+) from the intracellular stores. Permeabilized VSMC loaded with (45)Ca(2+) were subjected to 7.5% average (15% maximal) cyclical stretch. This resulted in an increase in (45)Ca(2+) rate constant by 0.126 +/- 0.0035. Inhibition of inositol 1,4,5-trisphosphate (IP(3)), ryanodine, and nicotinic acid adenine dinucleotide phosphate channels (NAADP) with 50 microg/ml heparin, 50 microM ruthenium red, and 25 microM thio-NADP, respectively, did not block the increase in (45)Ca(2+) efflux in response to cyclical stretch. However, 10 microM lanthanum, 10 microM gadolinium, and 10 microM cytochalasin D but not 10 microM nocodazole inhibited the increase in (45)Ca(2+) efflux. This supports the existence of a novel stretch-sensitive intracellular Ca(2+) store in VSMC that is distinct from the IP(3)-, ryanodine-, and NAADP-sensitive stores.
Mohanty
Madhumita Jena
MJ
Department of Medicine, Wayne State University School of Medicine and John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan 48201, USA. jenam@intmed.wayne.edu
Li
Xingli
X
D000199:Actins / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D004351:Drug Resistance; D005682:Gadolinium / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000378:metabolism; D007473:Ion Channels / Q000037:antagonists & inhibitors; D007811:Lanthanum / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D012433:Ryanodine / Q000378:metabolism; D013314:Stress, Mechanical
D000199:Actins; D015220:Calcium Channels; D007473:Ion Channels; D012433:Ryanodine; D015638:Cytochalasin D; D009249:NADP; C024376:NAADP; D007811:Lanthanum; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D005682:Gadolinium; D015739:Nocodazole; D002118:Calcium