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

Modulation of intracellular calcium ([Ca 2+ ] i ) transient in response to β-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 β-adrenoceptor responsiveness were then studied. Mean arterial blood pressure, left ventricular pressure (LVP), systolic function [maximum positive change in pressure over time (+dP/d t max )], and diastolic function [maximum negative change in pressure over time (−dP/d t max )] were monitored during the in vivo experiment. β-Adrenoceptor density was quantitated by radioactive ligand binding. Single rat ventricular myocyte was obtained by enzymatic dissociation method. ±dP/d t max , myocyte contraction, intracellular [Ca 2+ ] i transient, and L-type calcium current in response to β-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/d t max were significantly reduced. LVP and ±dP/d t max were significantly attenuated in the HLU group in response to isoproterenol administration. In the in vitro study, the β-adrenoceptor density was unchanged. Effects of isoproterenol on electrically induced single-cell contraction and [Ca 2+ ] i transient in myocytes of ventricles in HLU rats were significantly attenuated. The enhanced L-type Ca 2+ current elicited by isoproterenol in cardiomyocytes was significantly decreased in the HLU group. The above results indicate that impaired function of L-type Ca 2+ current and decreased [Ca 2+ ] i transient cause the depressed responsiveness of the β-adrenoceptor stimulation, which may be partially responsible for the depression of cardiac function.