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Am J Physiol Cell Physiol 283: C456-C462, 2002. First published May 15, 2002; doi:10.1152/ajpcell.00057.2002
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Vol. 283, Issue 2, C456-C462, August 2002

Stretch-induced Ca2+ release via an IP3-insensitive Ca2+ channel

Madhumita Jena Mohanty and Xingli Li

Department of Medicine, Wayne State University School of Medicine and John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan 48201

Various mechanical stimuli increase the intracellular Ca2+ concentration ([Ca2+]i) in vascular smooth muscle cells (VSMC). A part of the increase in [Ca2+]i is due to the release of Ca2+ from intracellular stores. We have investigated the effect of mechanical stimulation produced by cyclical stretch on the release of Ca2+ from the intracellular stores. Permeabilized VSMC loaded with 45Ca2+ were subjected to 7.5% average (15% maximal) cyclical stretch. This resulted in an increase in 45Ca2+ rate constant by 0.126 ± 0.0035. Inhibition of inositol 1,4,5-trisphosphate (IP3), ryanodine, and nicotinic acid adenine dinucleotide phosphate channels (NAADP) with 50 µg/ml heparin, 50 µM ruthenium red, and 25 µM thio-NADP, respectively, did not block the increase in 45Ca2+ efflux in response to cyclical stretch. However, 10 µM lanthanum, 10 µM gadolinium, and 10 µM cytochalasin D but not 10 µM nocodazole inhibited the increase in 45Ca2+ efflux. This supports the existence of a novel stretch-sensitive intracellular Ca2+ store in VSMC that is distinct from the IP3-, ryanodine-, and NAADP-sensitive stores.

stretch; calcium; vascular smooth muscle cells; inositol 1,4,5-trisphosphate; ryanodine


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