Effect of aminophylline on mechanical activity of rat diaphragm bundles

We studied the effect of aminophylline (0.1-1 mM) on the mechanical and electrical activity of rat diaphragm bundles in vitro (25 degrees C). The main findings are the following. 1) Aminophylline potentiates the twitch tension. The tetanus tension is not modified, although the rate of decay is decreased. 2) The relation between K contracture tension and resting membrane potential (Vm) is shifted toward more negative values of the Vm in the aminophylline-containing solution. 3) The mechanical threshold measured by direct visualization of the fiber is also lowered in the fibers equilibrated in aminophylline. These effects are reversible by washing out the preparation with normal solution. 4) The shift in the relation between tension and Vm induced by aminophylline is reversed by 1 microM nifedipine. 5) The generation of action potential is not modified by aminophylline. We suggest that the shift in the mechanical threshold is the principal factor involved in the potentiating effect of aminophylline. We speculate that theophylline acts to augment tension by enhancing calcium release from the sarcoplasmic reticulum and that nifedipine blocks this release (E. Rios, and G. Brum. Nature Lond. 325: 717-720, 1987).