Inositol trisphosphate releases stored calcium to block voltage-dependent calcium channels in single smooth muscle cells

Abstract

In single cells obtained by enzymic treatment of rabbit small-intestinal smooth muscle, and held under voltage clamp by patch pipette in the whole-cell recording mode, release of inositol trisphosphate (InsP3) from its caged precursor by flash photolysis caused complete inhibition of the voltage-dependent calcium current. No inhibition was seen in control experiments where the cage (2-nitrosoacetophenone) was released by flash photolysis from caged ATP. The inhibition by InsP3 of the calcium current was prevented if 10 mM EGTA or 2 mg/ml heparin was included in the pipette solution. Heparin is known to block InsP3 receptors. These results suggest that release of calcium stores by InsP3 raises Cai and that calcium ions inhibit the calcium current by acting either directly or otherwise on the internal mouth of the calcium channel.