Differential regulation of L-type Ca2+ channels in cerebral and mesenteric arteries after simulated microgravity in rats and its intervention by standing

Abstract

This study was designed to clarify whether simulated microgravity can induce differential changes in the current and protein expression of the L-type Ca2+ channel (CaL) in cerebral and mesenteric arteries and whether these changes can be prevented by daily short-duration −Gx exposure. Tail suspension [hindlimb unloading (HU)] for 3 and 28 days was used to simulate short- and medium-term microgravity-induced deconditioning effects. Standing (STD) for 1 h/day was used to provide −Gx as a countermeasure. Whole cell patch-clamp experiments revealed an increase in current density of CaL of vascular smooth muscle cells (VSMCs) isolated from cerebral arteries of rats subjected to HU and a decrease in VSMCs from mesenteric arteries. Western blot analysis revealed a significant increase and decrease of CaL channel protein expression in cerebral and small mesenteric arterial VSMCs, respectively, only after 28 days of HU. STD for 1 h/day did not prevent the increase of CaL current density in cerebral arterial VSMCs, but it prevented completely (within 3 days) and partially (28 days) the decrease of CaL current density in small mesenteric arterial VSMCs. Consistent with the changes in CaL current, STD for 1 h/day did not prevent the increase of CaL expression in cerebrovascular myocytes but did prevent the reduction of CaL expression in mesenteric arterial VSMCs subjected to 28 days of HU. These data indicate that simulated microgravity up- and downregulates the current and expression of CaL in cerebral and hindquarter VSMCs, respectively. STD for 1 h/day differentially counteracted the changes of CaL function and expression in cerebral and hindquarter arterial VSMCs of HU rats, suggesting the complexity of the underlying mechanisms in the effectiveness of intermittent artificial gravity for prevention of postflight cardiovascular deconditioning, which needs further clarification.