Sex differences in mitochondrial Ca2+ handling in mouse fast-twitch skeletal muscle in vivo.

We investigated sex differences in mitochondrial Ca²⁺ handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca²⁺ 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 μMat 10 min intervals). Thirty minutes after treatment, [Ca²⁺]cyto was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca²⁺]cyto in male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 M carbonyl cyanide-4- (trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca²⁺ uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca²⁺]cyto increase. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared with males (mitochondria number: 13.1 ± 1.0 in males vs. 19.9 ± 2.3 in females; mitochondrial volume: 0.034 ± 0.004 μm3/μm3 fiber volume in males vs. 0.066 ± 0.008 μm3/μm3 fiber volume in females, both P < 0.05). There were no sex differences in the content of SR Ca²⁺-ATPase, mitochondrial Ca²⁺ uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that 1) mitochondrial Ca²⁺ uptake ability is greater in female than male myocytes, and 2) this superior Ca²⁺ uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content but not to the expression of mitochondrial proteins related to mitochondrial Ca²⁺ uptake. [ABSTRACT FROM AUTHOR]