Modulation of intracellular calcium transient in response to β-adrenoceptor stimulation in the hearts of 4-wk-old rats during simulated weightlessness

Cui Y, Zhang S-M, Zhang Q-Y, Fan R, Li J, Guo H-T, Bi H, Wang Y-M, Hu Y-Z, Zheng Q-J, Gu C-H, Yu S-Q, Yi D-H, Li Z-C, Pei J-M. Modulation of intracellular calcium transient in response to beta-adrenoceptor stimulation in the hearts of 4-wk-old rats during simulated weightlessness. J Appl Physiol 108: 838-844, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01055.2009.-Modulation of intracellular calcium ([Ca2+](i)) transient in response to beta-adrenoceptor stimulation in the hearts of hindlimb unweighted (HLU) rats during simulated weightlessness has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness. Effects of simulated microgravity on beta-adrenoceptor responsiveness were then studied. Mean arterial blood pressure, left ventricular pressure (LVP), systolic function [maximum positive change in pressure over time (+dP/dt(max))], and diastolic function [maximum negative change in pressure over time (-dP/dt(max))] were monitored during the in vivo experiment. beta-Adrenoceptor density was quantitated by radioactive ligand binding. Single rat ventricular myocyte was obtained by enzymatic dissociation method. +/-dP/dt(max), myocyte contraction, intracellular [Ca2+](i) transient, and L-type calcium current in response to beta-adrenoceptor stimulation with isoproterenol were measured. Compared with the control group, no significant changes were found in heart weight, body weight, and mean arterial blood pressure, whereas LVP and +/-dP/dt(max) were significantly reduced. LVP and +/-dP/dt(max) were significantly attenuated in the HLU group in response to isoproterenol administration. In the in vitro study, the beta-adrenoceptor density was unchanged. Effects of isoproterenol on electrically induced single-cell contraction and [Ca2+](i) transient in myocytes of ventricles in HLU rats were significantly attenuated. The enhanced L-type Ca2+ current elicited by isoproterenol in cardiomyocytes was significantly decreased in the HLU group. The above results indicate that impaired function of L-type Ca2+ current and decreased [Ca2+](i) transient cause the depressed responsiveness of the beta-adrenoceptor stimulation, which may be partially responsible for the depression of cardiac function.