Analysis of catecholamine effects in single atrial trabeculae of the frog heart.

Abstract

A study was made of the time course of the effects of adrenaline and isoprenaline on both twitch tension and the intracellular action potential of single atrial trabeculae from frog heart, under a variety of experimental conditions. Twitch tension and overshoot of action potentials rose and subsided in a parallel fashion during build-up and decline of catecholamine action. Cessation of stimulation during drug application had little effect on the tension responses to the drugs. These, and also results obtained with step changes of external calcium concentration during drug exposure, suggest that tension enhancement is a direct consequence of the increased calcium inward current produced by the catecholamines. Exceptional results from trabeculae of ‘hypodynamic’ hearts are described and interpreted on the basis of previous findings obtained in the ‘hypo-dynamic’ condition. Under suitable conditions, including the use of brief periods of drug exposure (≤20 s), three phases of ( β -catecholamine action were discernible: (1) a latency period, of up to 15 s, which preceded tension and potential rise after drug application. Results are presented suggesting that this latency mainly reflects the time which it takes for drug-combined receptors to activate adenylate cyclase in the cell membrane. (2) A sub­sequent phase was critically dependent, in both its magnitude and time course, on phosphodiesterase activity, as was shown by the application of the specific inhibitors papaverine, ICI 63 197, and Ro 20-1724. This phase is probably controlled by the build-up and decline of cAMP within the cells and the subsequent activation and deactivation of a protein kinase. (3) A third phase, associated with the final portion of the decline of catecholamine action, was relatively insensitive to moderate inhi­bition of phosphodiesterase activity. It is attributed to a change of phosphorylation of sites at the internal surface of the cell membrane, the process which, it is assumed, determines the size of calcium inward current during an action potential. Tension decline after a short staircase occurred with a time course closely similar to that of the final phase of the declining catecholamine response. A common final step in the sequential cellular processes under­ lying the two responses is proposed. In some 40% of the trabeculae examined, adrenaline responses were of ‘mixed’ origin: in addition to the relatively slow β -adrenergic action, an initial rapid tension change was present, and experimental tests suggest that this is mediated by α -type receptors.