Research Article: Store-Operated Ca2+ Entry (SOCE) Contributes to Normal Skeletal Muscle Contractility in young but not in aged skeletal muscle

Date Published: June 6, 2011

Publisher: Impact Journals LLC

Author(s): Angela M Thornton, Xiaoli Zhao, Noah Weisleder, Leticia S. Brotto, Sylvain Bougoin, Thomas M. Nosek, Michael Reid, Brian Hardin, Zui Pan, Jianjie Ma, Jerome Parness, Marco Brotto.

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Abstract

Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skeletal muscle, particularly at high frequency stimulation, and such effects were completely absent in aged skeletal muscle. Our data indicate that SOCE contributes to the normal physiological contractile response of young healthy skeletal muscle and that defective extracellular Ca2+ entry through SOCE contributes to the reduced contractile force characteristic of aged skeletal muscle.

Partial Text

Aging is a complex biological process marked by the gradual decline of a multitude of physiological processes [1-5]. Some functional changes, such as decreased muscular strength, have a tremendous impact on the quality of life. Normal aging involves sarcopenia, a combination of atrophy and decreased muscular strength that develops despite dietary interventions and increased physical activity [6, 7]. The physical, psychological and socio-economic impact of sarcopenia is largely underestimated despite the fact that it is a leading contributor to debilitating injuries due to repetitive falls, loss of independence, and a reduced quality of life in the elderly population [4]. Understanding the cellular mechanisms that contribute to sarcopenia is essential for the development of effective treatments and improved care for the elderly.

As aging populations grow world-wide (It has been estimated that by 2050 more than 200 million humans will have sarcopenia), the aging-related decline in muscle function becomes a more pressing public health concern that requires more effective therapeutic approaches, which in turn requires an understanding of sarcopenia at a mechanistic level. While a portion of the decrease in muscular strength during aging can be explained by muscle atrophy, it is clear that other components contribute to reduced force production during aging. Furthermore, it is unquestionable that an array of cellular modifications [8-13] may contribute to muscle aging, and the pleiotropic nature of muscle aging muscle be recognized and accepted if we are to make significant progress towards its prevention and management.

 

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