Age-associated Changes in /3-Adrenergic Modulation on Rat Cardiac Excitation-Contraction Coupling

Previous studies have demonstrated that the ability of (.-adrenergic receptor (.BAR) stimulation to increase cardiac contractility declines with aging. In the present study, the control mechanisms of excitation-contraction (EC) cou-pling, including calcium current (Ice), cytosolic Ca2 " (Ca?') transient and contraction in response to BAR stimulation were investigated in ventricular myocytes isolated from rat hearts of a broad age range (2, 6-8, and 24 mo). While the baseline contractile performance and the Ca? ' transient did not differ markedly among cells from hearts of all age groups, the responses of the Ca; ' transient and contraction to fi-adrenergic stimulation by norepinephrine (NE) dimin-ished with aging: the threshold concentration and the EDSO increased in rank order with aging; the maximum responses of contraction and Cai+ transient decreased with aging. Fur-thermore, the efficacy of fiAR stimulation to increase 1C. was significantly reduced with aging, and the diminished responses of the contraction and Ca? ' transient amplitudes to NE were proportional to the reductions in the Ic re-sponse. These findings suggest that the observed age-associ-ated reduction in fAR modulation of the cardiac contrac-tion is, in part at least, due to a deficit in modulation of Ca?+, particularly the activity of L-type calcium channels. (J. Clin. Invest. 1994. 94:2051-2059.) Key words: aging * 13-adrenergic receptor * calcium current * cytosolic calcium-contractio