Sex differences in mitochondrial Ca 2+ handling in mouse fast-twitch skeletal muscle in vivo

• Published in: Journal of applied physiology (1985) 2020-02, Vol.128 (2), p.241-251
• Main Authors: Watanabe, Daiki, Hatakeyama, Koji, Ikegami, Ryo, Eshima, Hiroaki, Yagishita, Kazuyoshi, Poole, David C, Kano, Yutaka
• Format: Article
• Language: English
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.00230.2019

We investigated sex differences in mitochondrial Ca handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca concentration ([Ca ] ) 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) Ca -ATPase inhibitor] (from 10 to 30 to 50 μM at 10 min intervals). Thirty minutes after treatment, [Ca ] was increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca ] in male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca ] 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 μm /μm fiber volume in males vs. 0.066 ± 0.008 μm /μm fiber volume in females, both < 0.05). There were no sex differences in the content of SR Ca -ATPase, mitochondrial Ca uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that mitochondrial Ca uptake ability is greater in female than male myocytes, and this superior Ca 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 Ca uptake. This investigation presents evidence that female versus male fast-twitch muscle exhibits a greater mitochondrial calcium ion uptake capability that is partly conferred by the higher intermyofibrillar mitochondrial volume density.