The goal of the proposed studies is to test the hypothesis that activation of fast twitch skeletal muscles is regulated by altering the phosphorylation state of the ryanodine receptor (RyR) sarcoplasmic reticulum (SR) calcium release channels. In this project the investigator will use the back phosphorylation-fragmentation-derivatization (BFD) and fragmentation Western blot (frag-blot) methods to determine the in vivo phosphorylation stoichiometries of specific sites in the different RyR isoforms in vivo in nonactivated muscles, as well as during tetanic stimulation, and during moderate and severe fatigue. Rat extensor digitorum longus (EDL) and frog semitendinosus muscles will be compared o ascertain if phosphorylation of the RyRs differ in muscles containing different ratios of RyR isoforms. In addition, selected studies will be expanded to include rabbit and chicken muscles to test for interspecies variations between mammalian and nonmammalian species.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR045112-03
Application #
6375085
Study Section
Special Emphasis Panel (ZRG4-GMB (01))
Program Officer
Lymn, Richard W
Project Start
1999-05-01
Project End
2004-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
3
Fiscal Year
2001
Total Cost
$260,590
Indirect Cost
Name
University of Nevada Reno
Department
Pharmacology
Type
Schools of Medicine
DUNS #
146515460
City
Reno
State
NV
Country
United States
Zip Code
89557
Peng, S; Publicover, N G; Kargacin, G J et al. (2004) Imaging single cardiac ryanodine receptor Ca2+ fluxes in lipid bilayers. Biophys J 86:134-44
Peng, S; Publicover, N G; Airey, J A et al. (2004) Diffusion of single cardiac ryanodine receptors in lipid bilayers is decreased by annexin 12. Biophys J 86:145-51
Kogler, Gesine; Sensken, Sandra; Airey, Judith A et al. (2004) A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 200:123-35
Airey, Judith A; Almeida-Porada, Graca; Colletti, Evan J et al. (2004) Human mesenchymal stem cells form Purkinje fibers in fetal sheep heart. Circulation 109:1401-7
Tanna, Bhavna; Welch, William; Ruest, Luc et al. (2003) An anionic ryanoid, 10-O-succinoylryanodol, provides insights into the mechanisms governing the interaction of ryanoids and the subsequent altered function of ryanodine-receptor channels. J Gen Physiol 121:551-61