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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1567.)
© 2003 American Heart Association, Inc.

Vascular Biology

Crucial Role of Type 2 Inositol 1,4,5-Trisphosphate Receptors for Acetylcholine-Induced Ca²⁺ Oscillations in Vascular Myocytes

Jean-Luc Morel^*; Nicolas Fritz^*; Jean-Louis Lavie; Jean Mironneau

From Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017, Université Bordeaux 2, Bordeaux, France.

Correspondence to Jean Mironneau, Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. E-mail jean.mironneau{at}umr5017.u-bordeaux2.fr

Objective— The aim of this study was to correlate the expression of InsP₃R subtypes in native vascular and visceral myocytes with specific Ca²⁺-signaling patterns.

Methods and Results— By Western blot and immunostaining, we showed that rat portal vein expressed InsP₃R1 and InsP₃R2 but not InsP₃R3, whereas rat ureter expressed InsP₃R1 and InsP₃R3 but not InsP₃R2. Acetylcholine induced single Ca²⁺ responses in all ureteric myocytes but only in 50% of vascular myocytes. In the remaining vascular myocytes, the first transient peak was followed by Ca²⁺ oscillations. By correlating Ca²⁺ signals and immunostaining, we revealed that oscillating vascular cells expressed both InsP₃R1 and InsP₃R2 whereas nonoscillating vascular cells expressed only InsP₃R1. Acetylcholine-induced oscillations were not affected by inhibitors of ryanodine receptors, Ca²⁺-ATPases, Ca²⁺ influx, and mitochondrial Ca²⁺ uniporter but were inhibited by intracellular infusion of heparin. Using specific antibodies against InsP₃R subtypes, we showed that acetylcholine-induced Ca²⁺ oscillations were specifically blocked by the anti-InsP₃R antibody. These data were supported by antisense oligonucleotides targeting InsP₃R2, which selectively inhibited Ca²⁺ oscillations.

Conclusions— Our results suggest that in native smooth muscle cells, a differential expression of InsP₃R subtypes encodes specific InsP₃-mediated Ca²⁺ responses and that the presence of the InsP₃R2 subtype is required for acetylcholine-induced Ca²⁺ oscillations in vascular myocytes.

Key Words: calcium • InsP₃-gated channel • Ca²⁺ oscillations • smooth muscle • acetylcholine

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