Effects of Ca2+ and catecholamines on the guinea pig atrium action potential plateau.

The activation process in isolated electrically driven guinea pig atria was studied by means of simultaneous microelectrode and tension recording. Reducing external calcium from 2.5 to 1.25 mM prolonged the plateau but further reduction of calcium shortened it. Progressively increasing doses of the calcium antagonist D600 (up to 1.4 micrometer), however, monotonically decreased plateau duration. Either protocol monotonically decreased steady-state tension, but with markedly different effects on the restitution relation. Epinephrine, and to a lesser extent isoproterenol, restored plateau duration after exposure to either a calcium-free or D600-containing solution, but only the isoproterenol effect was propranolol sensitive. Addition of calcium chelators enhanced rather than prevented the effect of epinephrine on plateau duration in a calcium-free solution, extending the plateau duration to more than 3 times normal in some cases. These results are explained in terms of two opposing effects of a change in calcium concentration on plateau formation, one action being through the slow inward current and the second through a shift in a calcium dependence of the inward-rectifying, potassium conductance system.