Norepinephrine-induced Ca(2+) waves depend on InsP(3) and ryanodine receptor activation in vascular myocytes.
In rat portal vein myocytes, Ca(2+) signals can be generated by inositol 1,4,5-trisphosphate (InsP(3))- and ryanodine-sensitive Ca(2+) release channels, which are located on the same intracellular store. Using a laser scanning confocal microscope associated with the patch-clamp technique, we showed that propagated Ca(2+) waves evoked by norepinephrine (in the continuous presence of oxodipine) were completely blocked after internal application of an anti-InsP(3) receptor antibody. These propagated Ca(2+) waves were also reduced by approximately 50% and transformed in homogenous Ca(2+) responses after application of an anti-ryanodine receptor antibody or ryanodine. All-or-none Ca(2+) waves obtained with increasing concentrations of norepinephrine were transformed in a dose-response relationship with a Hill coefficient close to unity after ryanodine receptor inhibition. Similar effects of the ryanodine receptor inhibition were observed on the norepinephrine- and ACh-induced Ca(2+) responses in non-voltage-clamped portal vein and duodenal myocytes and on the norepinephrine-induced contraction. Taken together, these results show that ryanodine-sensitive Ca(2+) release channels are responsible for the fast propagation of Ca(2+) responses evoked by various neurotransmitters producing InsP(3) in vascular and visceral myocytes.
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, Centre National de la Recherche Scientifique Enseignement Supérieur Associé 5017, Université de Bordeaux II, 33076 Bordeaux Cedex, France.
F X
FX
Boittin
N
N
Macrez
G
G
Halet
J
J
Mironneau
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
D018377:Neurotransmitter Agents; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium; D009638:Norepinephrine