Crucial role of type 2 inositol 1,4,5-trisphosphate receptors for acetylcholine-induced Ca2+ oscillations in vascular myocytes

J.-L. Morel
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003-09-01; 23(9): 1567-1575
DOI: 10.1161/01.ATV.0000089013.82552.5D

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1. Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1567-75. Epub 2003 Jul 31.

Crucial role of type 2 inositol 1,4,5-trisphosphate receptors for
acetylcholine-induced Ca2+ oscillations in vascular myocytes.

Morel JL(1), Fritz N, Lavie JL, Mironneau J.

Author information:
(1)Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR 5017,
Université Bordeaux 2, Bordeaux, France.

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.

DOI: 10.1161/01.ATV.0000089013.82552.5D
PMID: 12893684 [Indexed for MEDLINE]

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