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

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 Ca-45(2+) were subjected to 7.5% average (15% maximal) cyclical stretch. This resulted in an increase in Ca-45(2+) 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 mug/ml heparin, 50 muM ruthenium red, and 25 muM thio-NADP, respectively, did not block the increase in Ca-45(2+) efflux in response to cyclical stretch. However, 10 muM lanthanum, 10 muM gadolinium, and 10 muM cytochalasin D but not 10 muM nocodazole inhibited the increase in Ca-45(2+) 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.