The Mu class glutathione transferase is abundant in striated muscle and is an isoform-specific regulator of ryanodine receptor calcium channels.
Members of the glutathione transferase (GST) structural family are novel regulators of cardiac ryanodine receptor (RyR) calcium channels. We present the first detailed report of the effect of endogenous muscle GST on skeletal and cardiac RyRs. An Mu class glutathione transferase is specifically expressed in human muscle. An hGSTM2-2-like protein was isolated from rabbit skeletal muscle and sheep heart, at concentrations of approximately 17-93 microM. When added to the cytoplasmic side of RyRs, hGSTM2-2 and GST isolated from skeletal or cardiac muscle, modified channel activity in an RyR isoform-specific manner. High activity skeletal RyR1 channels were inactivated at positive potentials or activated at negative potentials by hGSTM2-2 (8-30 microM). Inactivation became faster as the positive voltage was increased. Channels recovered from inactivation when the voltage was reversed, but recovery times were significantly slowed in the presence of hGSTM2-2 and muscle GSTs. Low activity RyR1 channels were activated at both potentials. In contrast, hGSTM2-2 and GSTs isolated from muscle (1-30 microM) in the cytoplasmic solution, caused a voltage-independent inhibition of cardiac RyR2 channels. The results suggest that the major GST isoform expressed in muscle regulates Ca2+ signalling in skeletal and cardiac muscle and conserves Ca2+ stores in the sarcoplasmic reticulum.
Abdellatif
Yasser
Y
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra City, ACT 2601, Australia.
Liu
Dan
D
Gallant
Esther M
EM
Gage
Peter W
PW
Board
Philip G
PG
Dulhunty
Angela F
AF
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008051:Lipid Bilayers; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D009206:Myocardium / Q000378:metabolism; D020033:Protein Isoforms / Q000302:isolation & purification / Q000378:metabolism; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012756:Sheep; D013997:Time Factors
D008051:Lipid Bilayers; D020033:Protein Isoforms; D019837:Ryanodine Receptor Calcium Release Channel; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2