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.