Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats

Morel, Jean-Luc; Dabertrand, Fabrice; Porte, Yves; Prévot, Anne; Macrez, Nathalie

doi:10.1007/s00424-013-1387-9

Back

Journal article

Up-regulation of ryanodine receptor expression increases the calcium-induced calcium release and spontaneous calcium signals in cerebral arteries from hindlimb unloaded rats

Morel, Jean-Luc Institut des Maladies Neurodénératives, UMR 5293, Bordeaux, France - Institut des Maladies Neurodégénératives, UMR 5293, Universite de Bordeaux, France
Dabertrand, Fabrice Department of Pharmacology, UVM College of University of Vermont, Burlington, VT, USA
Porte, Yves Institut des Maladies Neurodégénératives, UMR 5293, Universite de Bordeaux, France
Prévot, Anne Department of Medicine/Physiology, Université de Fribourg, Switzerland
Macrez, Nathalie Institut des Maladies Neurodégénératives, UMR 5293, CNRS, Bordeaux, France

01.08.2014

Published in:

Pflügers Archiv - European Journal of Physiology. - 2014, vol. 466, no. 8, p. 1517–1528

English 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.

Faculty

Faculté des sciences et de médecine

Department

Département de Médecine

Language