Age-associated changes in β-adrenergic modulation on rat cardiac excitation-contraction coupling

Previous studies have demonstrated that the ability of β-adrenergic receptor (βAR) stimulation to increase cardiac contractility declines with aging. In the present study, the control mechanisms of excitation-contraction (EC) coupling, including calcium current (I(Ca)), cytosolic Ca²⁺ (Ca(i)/²⁺) transient and contraction in response to βAR 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(i)/²⁺ transient did not differ markedly among cells from hearts of all age groups, the responses of the Ca(i)/²⁺ transient and contraction to β- adrenergic stimulation by norepinephrine (NE) diminished with aging: the threshold concentration and the ED₅₀ increased in rank order with aging; the maximum responses of contraction and Ca(i)/²⁺ transient decreased with aging. Furthermore, the efficacy of βAR stimulation to increase I(Ca) was significantly reduced with aging, and the diminished responses of the contraction and Ca(i)/²⁺ transient amplitudes to NE were proportional to the reductions in the I(Ca) response. These findings suggest that the observed age-associated reduction in βAR modulation of the cardiac contraction is, in part at least, due to a deficit in modulation of Ca(i)/²⁺, particularly the activity of L-type calcium channels.