Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin

Eva R. Chin, Robert W. Grange, Francois Viau, Alain R. Simard, Caroline Humphries, John Shelton, Rhonda Bassel-Duby, R. Sanders Williams, Robin N. Michel

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58% type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 ± 2.6 vs. 55.1 ± 4.7 ms; half-relaxation time: 42.1 ± 3.5 vs. 68.1 ± 9.6 ms, P < 0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 ± 0.4% in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64% reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.

Original languageEnglish (US)
Pages (from-to)649-663
Number of pages15
JournalJournal of Physiology
Volume547
Issue number2
DOIs
StatePublished - Mar 1 2003

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Parvalbumins
Transgenic Mice
Phenotype
Muscles
Myosin Heavy Chains
Calcineurin
Proteins
Slow-Twitch Muscle Fibers
Glycerolphosphate Dehydrogenase
Contractile Proteins
Ryanodine Receptor Calcium Release Channel
Succinate Dehydrogenase
Metabolome
Muscle Proteins
Skeletal Muscle
Messenger RNA
Genes

ASJC Scopus subject areas

  • Physiology

Cite this

Chin, E. R., Grange, R. W., Viau, F., Simard, A. R., Humphries, C., Shelton, J., ... Michel, R. N. (2003). Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin. Journal of Physiology, 547(2), 649-663. https://doi.org/10.1113/jphysiol.2002.024760

Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin. / Chin, Eva R.; Grange, Robert W.; Viau, Francois; Simard, Alain R.; Humphries, Caroline; Shelton, John; Bassel-Duby, Rhonda; Williams, R. Sanders; Michel, Robin N.

In: Journal of Physiology, Vol. 547, No. 2, 01.03.2003, p. 649-663.

Research output: Contribution to journalArticle

Chin, ER, Grange, RW, Viau, F, Simard, AR, Humphries, C, Shelton, J, Bassel-Duby, R, Williams, RS & Michel, RN 2003, 'Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin', Journal of Physiology, vol. 547, no. 2, pp. 649-663. https://doi.org/10.1113/jphysiol.2002.024760
Chin, Eva R. ; Grange, Robert W. ; Viau, Francois ; Simard, Alain R. ; Humphries, Caroline ; Shelton, John ; Bassel-Duby, Rhonda ; Williams, R. Sanders ; Michel, Robin N. / Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin. In: Journal of Physiology. 2003 ; Vol. 547, No. 2. pp. 649-663.
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abstract = "The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58{\%} type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 ± 2.6 vs. 55.1 ± 4.7 ms; half-relaxation time: 42.1 ± 3.5 vs. 68.1 ± 9.6 ms, P < 0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 ± 0.4{\%} in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64{\%} reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.",
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AU - Humphries, Caroline

AU - Shelton, John

AU - Bassel-Duby, Rhonda

AU - Williams, R. Sanders

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AB - The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58% type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 ± 2.6 vs. 55.1 ± 4.7 ms; half-relaxation time: 42.1 ± 3.5 vs. 68.1 ± 9.6 ms, P < 0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 ± 0.4% in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64% reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.

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