LAUSR

We investigated sex differences in mitochondrial Ca2+handling properties in mouse fast twitch skeletal muscle. Changes in cytoplasmicCa2+concentration ([Ca2+]cyto) were measured in vivo using tibialis anterior muscles from male and female mice. The muscles were exposed to increasing concentrations of cyclopiazonic acid [CPA; sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitor] (from 10 to 30 to 50 μM at 10 min intervals). Thirty min after treatment, [Ca2+]cyto was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca2+]cytoin male and female muscles, respectively, and there was a significant difference between sexes. However, muscle pre-incubation for 5 min with 10 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP; an inhibitor of mitochondria Ca2+uptake), eradicated this difference between sexes with respect to the CPA-induced [Ca2+]cytoincrease. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared to males (mitochondria number: 13.1 ±1.0 in male vs. 19.9 ±2.3 in female; mitochondrial volume: 0.034 ± 0.004 μm3/μm3fiber volume in male vs. 0.066 ±0.008 μm3/μm3fiber volume in female, both P<0.05). There were no sex differences in the content of SR Ca2+-ATPase, mitochondrial Ca2+uniporter (MCU),mitofusin (Mfn) 1 or Mfn2. These results suggest that i)mitochondrial Ca2+uptake ability is greater in female than male myocytes, ii)this superior Ca2+uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content, but not theexpression of mitochondrial proteins related to mitochondrial Ca2+uptake.