EFFECT OF AMINOPHYLLINE ON THE CONTRACTION THRESHOLD OF RAT DIAPHRAGM FIBERS

We studied the effect of aminophylline (0.1-1 mM) on the contraction threshold (CT) of rat diaphragm fibers (25-degrees-C). The CT was measured by direct visualization (x200) of the fiber under current-clamp conditions. The main findings are the following: 1) Aminophylline lowers the CT, in a dose-dependent manner, toward more negative values of the resting membrane potential (V(m). 2) Dibutyryl adenosine 3',5'-cyclic monophosphate (2 mM) shifts the CT, although this change is smaller than in the presence of xanthine. 3) Tetracaine (1 mM), a drug that diminishes Ca release from the sarcoplasmic reticulum, reduces the shift induced by 1 mM aminophylline; this is partially overcome by increasing aminophylline concentration to 5 mM. 4) Hyperpolarization of the fibers shifts the CT to more negative V(m). We suggest that the displacement in the CT to more negative V(m) plays an important role in the potentiating effect of aminophylline. This could be the result of an enhancement of Ca release from the sarcoplasmic reticulum.