Acetylcholine-induced Ca2+ oscillations are modulated by a Ca2+ regulation of InsP3R2 in rat portal vein myocytes

Nicolas Fritz, Jean Mironneau, Nathalie Macrez, Jean-Luc Morel
Pflugers Arch - Eur J Physiol. 2007-11-20; 456(2): 277-283
DOI: 10.1007/s00424-007-0379-z

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1. Pflugers Arch. 2008 May;456(2):277-83. Epub 2007 Nov 20.

Acetylcholine-induced Ca2+ oscillations are modulated by a Ca2+ regulation of
InsP3R2 in rat portal vein myocytes.

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

Author information:
(1)Molecular Neurobiology, Medical Biochemistry and Biophysics, Karolinska
Institutet, Scheeles väg 2, 171 77 Stockholm, Sweden.

Oscillations of cytosolic Ca2+ levels are believed to have important roles in
various metabolic and signalling processes in many cell types. Previously, we
have demonstrated that acetylcholine (ACh) evokes Ca2+ oscillations in vascular
myocytes expressing InsP3R1 and InsP3R2, whereas transient responses are
activated in vascular myocytes expressing InsP3R1 alone. The molecular mechanisms
underlying oscillations remain to be described in these native smooth muscle
cells. Two major hypotheses are proposed to explain this crucial signalling
activity: (1) Ca2+ oscillations are activated by InsP3 oscillations; and (2) Ca2+
oscillations depend on the regulation of the InsP3R by both InsP3 and Ca2+. In
the present study, we used a fluorescent InsP3 biosensor and revealed that ACh
induced a transient InsP3 production in all myocytes. Moreover, steady
concentrations of 3F-InsP3, a poorly hydrolysable analogue of InsP3, and
pharmacological activation of PLC evoked Ca2+ oscillations. Increasing cytosolic
Ca2+ inhibited the ACh-induced calcium oscillations but not the transient
responses and strongly reduced the 3F-InsP3-evoked Ca2+ response in oscillating
cells but not in non-oscillating cells. These results suggest that, in native
vascular myocytes, ACh-induced InsP3 production is transient and Ca2+
oscillations depend on a Ca2+ modulation of InsP3R2.

DOI: 10.1007/s00424-007-0379-z
PMID: 18026983 [Indexed for MEDLINE]

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