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Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition

  • Muscle physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

The skeletal muscle ryanodine receptor Ca2+ release channel (RyR1), essential for excitation-contraction (EC) coupling, demonstrates a known developmentally regulated alternative splicing in the ASI region. We now find unexpectedly that the expression of the splice variants is closely related to fiber type in adult human lower limb muscles. We examined the distribution of myosin heavy chain isoforms and ASI splice variants in gluteus minimus, gluteus medius and vastus medialis from patients aged 45 to 85 years. There was a strong positive correlation between ASI(+)RyR1 and the percentage of type 2 fibers in the muscles (r = 0.725), and a correspondingly strong negative correlation between the percentages of ASI(+)RyR1 and percentage of type 1 fibers. When the type 2 fiber data were separated into type 2X and type 2A, the correlation with ASI(+)RyR1 was stronger in type 2X fibers (r = 0.781) than in type 2A fibers (r = 0.461). There was no significant correlation between age and either fiber-type composition or ASI(+)RyR1/ASI(−)RyR1 ratio. The results suggest that the reduced expression of ASI(−)RyR1 during development may reflect a reduction in type 1 fibers during development. Preferential expression of ASI(−) RyR1, having a higher gain of in Ca2+ release during EC coupling than ASI(+)RyR1, may compensate for the reduced terminal cisternae volume, fewer junctional contacts and reduced charge movement in type 1 fibers.

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Acknowledgments

The authors are grateful to Suzy Pace and to Joan Stivala for assistance with the collection of the human tissue and to NA Beard for helpful comment on the manuscript. The work was supported by grants from the National Health and Medical Research Council APP1020589 and APP1002589 as well as an Australian Postgraduate Award and a John Curtin School of Medical Research supplementary scholarship to HW.

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Authors and Affiliations

  1. John Curtin School of Medical Research, Australian National University, Acton, ACT, 2600, Australia

    Hermia Willemse, Angelo Theodoratos & Angela F. Dulhunty

  2. Trauma and Orthopaedic Research Unit, Canberra Hospital, Building 6, Level 1, P.O. Box 11, Woden, ACT, 2606, Australia

    Paul N. Smith

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  1. Hermia Willemse
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  2. Angelo Theodoratos
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Correspondence to Angela F. Dulhunty.

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Willemse, H., Theodoratos, A., Smith, P.N. et al. Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition. Pflugers Arch - Eur J Physiol 468, 269–278 (2016). https://doi.org/10.1007/s00424-015-1738-9

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