Inhibition of Ca2+ release in rat atrophied gastrocnemius muscle

Abstract

Contractile parameters of a twitch contraction and changes in these parameters during repetitive stimulation are modified by muscle atrophy induced by tetrodotoxin (TTX). These altered parameters include developed tension (DT), contraction time (t(c),), half-relaxation time (t(R, 1/4 )), average rate of force development (DT t(c)-1) and peak rate of relaxation (DT dt(min)-1. These modifications may be related to different Ca2+ concentration transients in the myoplasm during muscle stimulation. We have used dantrolene sodium (DS) in TTX-treated rat gastrocnemius muscle to test this hypothesis. In situ isometric contractile responses of rat gastrocnemius muscle during repetitive stimulation at 10 Hz were analysed before and after administration of DS. After DS administration, twitch amplitude, t(c), t(R, 1/4 ) and DT t(c)-1 decreased and DT dt(min)-1 relative to DT increased in atrophied muscle. During repetitive stimulation, a progressive enhancement in developed tension (staircase) was absent in atrophied muscle, but DT increased to 171 ± 4%, presenting a staircase response after DS treatment. This potentiation was accompanied by an increase in DT t(c)-1 to 175.6 ± 7%. Inhibition of Ca2+ release in atrophied muscle resulted in twitch contractile parameters and contractile responses to 10 Hz stimulation that were similar, in many respects, to those responses in control (non-atrophied) muscles.