Research Interests   Calcium signalling, ryanodine receptor structure and function

Research Description
My research is focused on a class of intracellular calcium channels--termed ryanodine receptors, or RyRs--that play a central role in controlling muscle contraction and the heart beat. Specific projects in the laboratory aim to determine

1) the molecular mechanisms of drugs that modulate these channels,
2) the effects channel mutations that underlie neuromuscular and cardiovascular disease,
3) the roles of channel accessory proteins, including calmodulin and FKBP, and
4) the basis of altered channel regulation during muscle fatigue and myocardial ischemia.

10. Fruen, B.R., Mickelson, J.R., and Louis, C.F. (1997) Dantrolene inhibition of sarcoplasmic reticulum Ca2+ release by direct and specific action at skeletal muscle ryanodine receptors. Journal of Biological Chemistry 272: 26965-26971.

11. Balog, E.M., Fruen, B.R., Kane, P.K., and Louis, C.F. (2000) Mechanisms of Pi regulation of the skeletal muscle SR Ca2+ release channel. American Journal of Physiology 278: C601-C611.

12. Fruen, B.R., Bardy, J., Byrem T.M., Strasburg G.M., and Louis, C.F. (2000) Differential Ca2+ sensitivity of skeletal and cardiac muscle ryanodine receptors in the presence of calmodulin. American Journal of Physiology 279(3): C724-C733.

13. Zhao, F., Li, P., Chen, S.R.W., Louis, C.F., and Fruen, B.R. (2001) Dantrolene inhibition of ryanodine receptor Ca2+ release channels: molecular mechanism and isoform selectivity. Journal of Biological Chemistry 276: 13810-13816.

14. Balog, E.M., Fruen, B.R., Shomer, N.H. and Louis, C.F. (2001) Divergent effects of the MHS Arg615Cys mutation on the Ca2+ and Mg2+ dependence of the RyR1. Biophysical Journal 81: 2050-2058.

15. Louis, C.F., Balog, E.M., and Fruen, B.R. (2001) Malignant hyperthermia: an inherited disorder of Ca2+ regulation in skeletal muscle (invited review). Bioscience Reports 21: 155-168.

16. Thomas, J.M., Summerhill, R.J., Fruen, B.R., Churchill, G.C., and Galione, A. (2002) Calmodulin mediates desensitisation of cyclic ADP-ribose-induced Ca2+ release. Current Biology, 12: 2018-2022.

17. Balog, E.M., Norton, L.E., Bloomquist, R.A., Bardy, J.M., Black, D.J., Louis, C.F., Thomas, D.D., and Fruen, B.R. (2002) Calmodulin oxidation alters functional interactions with RyR1 Ca2+ release channels: Role of critical Met residues. Journal of Biological Chemistry, 278: 15615-15621.

18. Fruen, B.R., Black, D.J., Bloomquist, R.A., Bardy, J.M., Johnson, J.D., Louis, C.F., and Balog, E.M. (2002) Regulation of the RYR1 and RYR2 Ca2+ release channel isoforms by Ca2+-insensitive mutants of calmodulin. Biochemistry, 42: 2740-2747.

19. Fruen BR, Balog EM, Schafer J, Nitu FR, Thomas DD, Cornea RL. 2005. Direct detection of calmodulin tuning by ryanodine receptor channel targets using a Ca2+-sensitive acrylodan-labeled calmodulin. Biochemistry.44: 278-84.

20. Balog EM, Norton LE, Thomas DD, Fruen BR. 2006. Role of calmodulin methionine residues in mediating productive association with cardiac ryanodine receptors. Am J Physiol Heart Circ Physiol. 290:H794-9.