title: Unexpected dependence of RyR1 splice variant expression in human lower limb muscles on fiber-type composition.
abstract: The skeletal muscle ryanodine receptor Ca(2+) 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 Ca(2+) 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.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Acton, ACT, 2600, Australia. Hermia.Willemse@canberra.edu.au.
authors.forename: Hermia
authors.initials: H
authors.lastname: Willemse
authors.affiliation: John Curtin School of Medical Research, Australian National University, Acton, ACT, 2600, Australia. angelo.theodoratos@anu.edu.au.
authors.forename: Angelo
authors.initials: A
authors.lastname: Theodoratos
authors.affiliation: Trauma and Orthopaedic Research Unit, Canberra Hospital, Building 6, Level 1, P.O. Box 11, Woden, ACT, 2606, Australia. psmith@orthoact.com.au.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Smith
authors.affiliation: John Curtin School of Medical Research, Australian National University, Acton, ACT, 2600, Australia. angela.dulhunty@anu.edu.au.
authors.forename: Angela F
authors.initials: AF
authors.lastname: Dulhunty
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007866:Leg / Q000033:anatomy & histology / Q000254:growth & development; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D018995:Myosin Heavy Chains
keywords: ASI splice variants; Aging; Fiber types; Human skeletal muscle; Ryanodine receptor