Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats
Pflugers Arch - Eur J Physiol. 2013-11-15; 466(8): 1517-1528
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1. Pflugers Arch. 2014 Aug;466(8):1517-28.
Up-regulation of ryanodine receptor expression increases the calcium-induced
calcium release and spontaneous calcium signals in cerebral arteries from
hindlimb unloaded rats.
Morel JL, Dabertrand F, Porte Y, Prevot A, Macrez N.
Microgravity induces a redistribution of blood volume. Consequently, astronauts’
body pressure is modified so that the upright blood pressure gradient is
abolished, thereby inducing a modification in cerebral blood pressure. This
effect is mimicked in the hindlimb unloaded rat model. After a duration of 8 days
of unloading, Ca2+ signals activated by depolarization and
inositol-1,4,5-trisphosphate intracellular release were increased in cerebral
arteries. In the presence of ryanodine and thapsigargin, the
depolarization-induced Ca2+ signals remained increased in hindlimb suspended
animals, indicating that Ca2+ influx and Ca2+-induced Ca2+ release mechanism were
both increased. Spontaneous Ca2+ waves and localized Ca2+ events were also
investigated. Increases in both amplitude and frequency of spontaneous Ca2+ waves
were measured in hindlimb suspension conditions. After pharmacological
segregation of Ca2+ sparks and Ca2+ sparklets, their kinetic parameters were
characterized. Hindlimb suspension induced an increase in the frequencies of both
Ca2+ localized events, suggesting an increase of excitability. Labeling with
bodipy compounds suggested that voltage-dependent Ca2+ channels and ryanodine
receptor expressions were increased. Finally, the expression of the ryanodine
receptor subtype 1 (RyR1) was increased in hindlimb unloading conditions. Taken
together, these results suggest that RyR1 expression and voltage-dependent Ca2+
channels activity are the focal points of the regulation of Ca2+ signals
activated by vasoconstriction in rat cerebral arteries with an increase of the
voltage-dependent Ca2+ influx.
PMID: 24233561 [Indexed for MEDLINE]