Robust store-operated calcium entry in aged mammalian skeletal muscle

J.N. Edwards,¹ D.F. Gilbert,² D.G. Blackmore,² R.M. Murphy³ and B.S. Launikonis,¹ ¹School of Biomedical Sciences, The University of Queensland, St Lucia, QLD 4072, Australia, ²Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia and ³Department of Zoology, La Trobe University, Melbourne, VIC 3086, Australia.

Store-operated Ca²⁺ entry (SOCE) is a specialized mechanism in muscle, involving extracellular Ca²⁺ entry in response to depleting intracellular Ca²⁺ stores during work. Although a report recently suggested SOCE is compromised in aged muscle (Zhao et al., 2008), we reassessed this with our novel, sensitive techniques (Launikonis & Ríos, 2007). Young (8-20 weeks) and aged (25 months) C57BL/10 mice from the same colony were compared for SOCE functionality and relevant protein abundances. Fluo-5N trapped in the tubular system of skinned fibres was imaged with confocal microscopy. Substitution of the standard intracellular solution with low Mg²⁺ solution induced Ca²⁺ release. There was initial Ca²⁺ uptake in sealed t-tubules, followed by depletion due to SOCE. SOCE deactivation followed Ca²⁺ reuptake into sarcoplasmic reticulum (SR) and reduction in myoplasmic Ca²⁺. Robust SOCE was observed in all fibres (n=8) from aged mice. In some fibres, subsequent Ca²⁺ waves were observed with defined onset of SOCE, allowing determination of SOCE activation kinetics. Whilst SOCE activation was delayed in aged (38±3.1 ms, n=4) compared to young (27±3.6 ms, n=6, p=0.044) muscle, SOCE deactivation was robust. Of note, rate of SR refilling compared to rate of SOCE deactivation varied between aged fibres (n=8). Furthermore, Orai1 and Stim1 protein levels were also varied suggesting the need for physiological and biochemical measurements on the same aged fibres. We conclude that SOCE continues to work in aged muscle but its deactivation and activation thresholds, as well as the integral SOCE protein levels may vary.

Zhao X, Weisleder N, Thornton A, Oppong Y, Campbell R, Ma J, Brotto M. (2008) Aging Cell 7: 561-568.

Launikonis BS, Ríos E. (2007) J. Physiol. 583: 81-97.