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.
Boittin
F X
FX
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.
Macrez
N
N
Halet
G
G
Mironneau
J
J
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