Modulation of calcium signalling by dominant negative splice variant of ryanodine receptor subtype 3 in native smooth muscle cells
Cell Calcium. 2006-07-01; 40(1): 11-21
DOI: 10.1016/j.ceca.2006.03.008
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1. Cell Calcium. 2006 Jul;40(1):11-21. Epub 2006 May 4.
Modulation of calcium signalling by dominant negative splice variant of ryanodine
receptor subtype 3 in native smooth muscle cells.
Dabertrand F(1), Morel JL, Sorrentino V, Mironneau J, Mironneau C, Macrez N.
Author information:
(1)Laboratoire de Signalisation et Interactions Cellulaires, CNRS UMR5017,
Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
The ryanodine receptor subtype 3 (RYR3) is expressed ubiquitously but its
physiological function varies from cell to cell. Here, we investigated the role
of a dominant negative RYR3 isoform in Ca2+ signalling in native smooth muscle
cells. We used intranuclear injection of antisense oligonucleotides to
specifically inhibit endogenous RYR3 isoform expression. In mouse duodenum
myocytes expressing RYR2 subtype and both spliced and non-spliced RYR3 isoforms,
RYR2 and non-spliced RYR3 were activated by caffeine whereas the spliced RYR3 was
not. Only RYR2 was responsible for the Ca2+-induced Ca2+ release mechanism that
amplified Ca2+ influx- or inositol 1,4,5-trisphosphate-induced Ca2+ signals.
However, the spliced RYR3 negatively regulated RYR2 leading to the decrease of
amplitude and upstroke velocity of Ca2+ signals. Immunostaining in injected cells
showed that the spliced RYR3 was principally expressed near the plasma membrane
whilst the non-spliced isoform was revealed around the nucleus. This study shows
for the first time that the short isoform of RYR3 controls Ca2+ release through
RYR2 in native smooth muscle cells.
DOI: 10.1016/j.ceca.2006.03.008
PMID: 16678258 [Indexed for MEDLINE]