Abstract

Calcitonin gene-related peptide (CGRP) acutely augments the contractile response of skeletal muscle to both direct and indirect stimulation. However, studies in whole muscle tissues have produced extremely variable results. To determine if differences in stimulation parameters are the source of this variation, the effects of increasing stimulus duration were evaluated in the isolated perfused rat hemidiaphragm. The effect of CGRP on the maximum force of contraction (Fc) was dependent upon the stimulus duration. CGRP (10(-6) M) produced an 11% increase in Fc with a 0.1-msec duration stimulus and a 32% increase with a 1.0-msec stimulus. In contrast, CGRP decreased the time for twitch relaxation and this effect was independent of stimulus duration. Additional studies demonstrated that CGRP shortened the relative refractory period. Compound muscle action potential recordings revealed that stimulus durations greater than 0.5 msec produced a second peak of electrical activity with an associated increased Fc. The effects of CGRP on Fc corresponded to the effects of CGRP on this second peak of compound muscle action potential activity. We conclude that, by decreasing the relative refractory period of the muscle tissue, CGRP enhances the potential for repetitive stimulation with commonly used experimental parameters.