The hypothesis advanced in this article requires further validation. Undoubtedly it will require modification as our knowledge of biochemical control increases. Nevertheless, it should prove useful in focusing attention on the apparent similarity in the response of a large number of specific cell types to particular stimuli. Emphasis has been placed on a few common and apparently key elements in these responses. It is recognized that other factors are undoubtedly involved. Specifically, the changes in membrane potentials indicate the likelihood of widespread changes in the properties of the cell membrane, for example, changes in Na(+) and K(+) transport and distribution. These aspects of cellular responses may eventually prove to be of equal or greater importance than those common aspects of the system already identified.

Cell Communication, Calcium Ion, and Cyclic Adenosine Monophosphate

Left ventricular pressure and volume during diastole reflect the interaction of ventricular elastic, viscous, and inertial properties, and the completeness of myocardial relaxation. Myocar...

Diastolic Properties of the Left Ventricle

The regulation of intracellular calcium

beta-Adrenergic stimulation of phospholamban phosphorylation and Ca2+-ATPase activity in guinea pig ventricles.

The effect of advanced age on the response of active tension, maximal rate of tension development (dT/dt), and contraction duration to catecholamines and to calcium was evaluated in isometric trabeculae carneae from young adult (6-month-old), middle-aged (12-month-old), and aged (25-month-old) rats. Control values were not age dependent except for that for contraction duration which was prolonged in the aged group. At a norepinephrine concentration of 8 times 10-5M, dT/dt increased to 163.8 plus or minus 5.3% of control in the young adult group and to 125.9 plus or minus 6.3% of control in the aged group (P smaller than 0.001). Active tension increased to 121.3 plus or minus 4.0% of control in the young adult muscles but did not increase in the aged muscles (P smaller than 0.01). Contraction duration shortened proportionately in both age groups. Similar results were obtained with isoproterenol. In contrast to the response to catecholamines, there was no age difference in the response of active tension and dT/dt to increasing concentrations of calcium. It is concluded that the intrinsic inotropic response to catecholamines is diminished in the aged myocardium. This finding does not appear to result from differences in tachyphylaxis, tissue uptake of catecholamines, or the ability of the contractile proteins to respond to increasing concentrations of calcium but instead may result from a decreased ability of catecholamines to increase the intracellular calcium available for contraction.

Diminished inotropic response of aged myocardium to catecholamines.

The mechanisms by which the catecholamines and glucagon increase myocardial contractility were investigated by studying the effects of cyclic 39, 59-AMP, epinephrine, and glucagon on calcium accumulation by a microsomal fraction of canine myocardium thought to represent sarcoplasmic reticulum, and by assaying the microsomal fraction for adenyl cyclase activity. Each agent produced a concentration-dependent increase in calcium accumulation. Moreover, adenyl cyclase, an enzyme activated by epinephrine and glucagon and responsible for the production of cyclic 39, 59-AMP, was present in the microsomal fraction. Its specific activity and responsiveness to epinephrine and glucagon were similar to that previously found in sarcolemmic fractions. The beta-receptor blocking agent propranolol abolished the activation of adenyl cyclase and increase in microsomal calcium accumulation produced by epinephrine, but was without effect when these same changes were produced by glucagon. These findings are consistent with the hypotheses that: (1) the positive inotropic effects of epinephrine and glucagon may occur as a result of an augmentation of the sarcotubular calcium pool(s); and (2) this effect is mediated, at least in part, by an elevation of cyclic 39, 59-AMP levels produced by activation of an adenyl cyclase localized to the sarcoplasmic reticulum.

Gerald S. Levey

Papers

Mechanism of Action of Epinephrine and Glucagon on the Canine Heart: EVIDENCE FOR INCREASE IN SARCOTUBULAR CALCIUM STORES MEDIATED BY CYCLIC 3',5'-AMP