Norepinephrine-induced Ca2+ waves depend on InsP3 and ryanodine receptor activation in vascular myocytes

In rat portal veinmyocytes, Ca²⁺ signals can begenerated by inositol 1,4,5-trisphosphate(InsP₃)- and ryanodine-sensitive Ca²⁺ release channels, which arelocated on the same intracellular store. Using a laser scanningconfocal microscope associated with the patch-clamp technique, weshowed that propagated Ca²⁺ wavesevoked by norepinephrine (in the continuous presence of oxodipine) werecompletely blocked after internal application of ananti-InsP₃ receptor antibody.These propagated Ca²⁺ waves werealso reduced by ~50% and transformed in homogenous Ca²⁺ responses after applicationof an anti-ryanodine receptor antibody or ryanodine. All-or-noneCa²⁺ waves obtained withincreasing concentrations of norepinephrine were transformed in adose-response relationship with a Hill coefficient close to unity afterryanodine receptor inhibition. Similar effects of the ryanodinereceptor inhibition were observed on the norepinephrine- andACh-induced Ca²⁺ responses innon-voltage-clamped portal vein and duodenal myocytes and on thenorepinephrine-induced contraction. Taken together, these results showthat ryanodine-sensitive Ca²⁺release channels are responsible for the fast propagation of Ca²⁺ responses evoked by variousneurotransmitters producing InsP₃ in vascular and visceral myocytes.