Time course of the increase in the myocardial slow inward current after a photochemically generated concentration jump of intracellular cAMP.

Abstract

Voltage-clamped atrial trabeculate from bullfrog hearts were exposed to membrane-permeant photolyzable o-nitrobenzyl esters of cAMP and cGMP. UV flashes produced intracellular concentration jumps of cAMP or cGMP. With the cAMP derivative, flashes resulted in an increased slow inward current (Isi), producing a broadened action potential. The Isi reached a maximum 10-30 s after the flash and decreased over the next 60-300 s. The 1st increases were observable within 150 ms; this value is an upper limit imposed by the instrumentation. Responses to flashes lasted longer at higher drug concentrations and in the presence of the phosphodiesterase inhibitor, papaverine; effects of flashes developed and decreased faster at higher temperature. Although the amplitude of the Isi was increased, its waveform and voltage sensitivity were not affected. Intracellular concentration jumps of cAMP failed to affect the muscarinic K+ conductance. There were no observable effects of cGMP concentration jumps. cAMP regulates the Isi. The 5- to 10-s delay between application of .beta.-agonists and the onset of positive inotropic effects observed in previous studies was correctly ascribed to events prior to the interaction between cAMP and protein kinase.