ACUTE EFFECTS OF CALCITONIN GENE-RELATED PEPTIDE ON THE MECHANICAL AND ELECTRICAL RESPONSES OF THE RAT HEMIDIAPHRAGM

Calcitonin gene-related peptide (CGRP) acutely augments the contractil e response of skeletal muscle to both direct and indirect stimulation. However, studies in whole muscle tissues have produced extremely vari able results. To determine if differences in stimulation parameters ar e the source of this variation, the effects of increasing stimulus dur ation were evaluated in the isolated perfused rat hemidiaphragm. The e ffect of CGRP on the maximum force of contraction (F(c)) was dependent upon the stimulus duration. CGRP (10(-6) M) produced an 11% increase in F(c) 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 relax ation and this effect was independent of stimulus duration. Additional studies demonstrated that CGRP shortened the relative refractory peri od. 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 F(c). The effects of CGRP on F(c ) 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 pot ential for repetitive stimulation with commonly used experimental para meters.