Injury of myofibers is common following unaccustomed stretches of activated skeletal muscles often leading to histopathologic changes thought to result from elevated intracellular calcium levels. The exact mechanism for the elevated calcium levels is not clear but stretch-activated ion channels have been proposed to play a role. PURPOSE: To examine if streptomycin, a blocker of stretch-activated ion channels, would attenuate muscle injury following a single bout of repeated stretches of activated dorsiflexor muscles to the same degree as treatment with EDTA, a calcium chelator. METHODS: Sprague Dawley rats (n = 6) were injected 3x daily for 8 days with streptomycin (S, 300 mg·kg-1·day-1 i.p.). Additional rats were given EDTA (n = 6, 150 mg·kg-1 i.p., 20 min before and 24 hours after the stretches); untreated rats (C, n = 6) served as controls. Using nerve stimulation, 40 stretches were imposed on isometric contractions [120 Hz, 0.2 ms pulse duration, 4.3 +/- 0.3 V (mean +/- SE)] by ankle rotation from 80° to 130° (velocity: 100 °·s-1, total stimulation time: 1 s, inter-stretch rest time: 40 s). Isometric force at an ankle position of 130° using stimulation frequencies of 20 Hz and 120 Hz was measured before and 10 minutes after the protocols. Using Azure A staining, necrotic myofibers were counted in cross-sections (thickness 8 µm) of the distal part of tibialis anterior (TA) muscles removed 48 hrs after the stretch protocols. RESULTS: Isometric force deficits, measured 10 minutes following the stretch protocol, were not different between groups at stimulation frequencies of 20 Hz (C: 55 +/- 4%, EDTA: 47 +/- 7%, S: 56 +/- 6%) and 120Hz (C: 11 +/- 3%, EDTA: 13 +/- 3%, S: 11 +/- 3%). Two days following the stretch protocol, TA wet weights increased by the same amount in all stretched muscles compared to the non-stretched side (C: 8.6 +/- 1.3%, EDTA: 7.3 +/- 1.0%, S: 8.1 +/- 2.2%). The number of muscle cells with histopathologic changes was significantly smaller in both streptomycin and EDTA-treated rats (C: 211 +/- 56, EDTA: 70 +/- 21, S: 38 +/- 4, p<0.05). CONCLUSION: Stretch-activated ion channels apparently play a role in the development of histopathologic changes from repeated stretches of activated skeletal muscles probably by increasing intracellular calcium.