James D. Fessenden, Ph.D.
Research Scientist
Ryanodine receptor structure-function
Email: fessenden at bbri.org

Research Summary
A key triggering step in striated muscle contraction is the release of Ca2+ from intracellular stores via activation of the ryanodine receptor (RyR).  The activity of this Ca2+ release channel is regulated by numerous associated proteins and pharmacological compounds.  We have previously characterized a molecular interaction site of 4-chloro-m-cresol (4-CmC), a potent RyR activator used for clinical diagnosis of the skeletal muscle disorder, malignant hyperthermia (MH).  Our long-term goal is to use 4-CmC to covalently attach conformationally-sensitive fluorescent probes to the RyR in order to define the dynamic structural changes of the RyR that occur during channel opening.  Using fluorescence resonance energy transfer (FRET) methods, we will eventually measure physical distances between defined locations on the RyR and its associated proteins (see figure).

Diagram depicting the ryanodine receptor (RyR) and its associated proteins.

Selected Publications
Paolini C, Fessenden JD, Pessah IN, Franzini-Armstrong C. Evidence for conformational coupling between two calcium channels. Proc Natl Acad Sci U S A. (2004) 101(34):12748-52.

Fessenden, J. D., Perez, C. F., Goth, S., Pessah, I. N., and Allen, P. D.  Identification of a key determinant of ryanodine receptor type 1 required for activation by 4-chloro-m-cresol.  J. Biol. Chem. 278 (2003) pp. 28727-28735.

Fessenden, J. D., Chen, L., Wang, Y., Paolini, C., Franzini-Armstrong, C., Allen, P. D., and Pessah, I. N.  Ryanodine receptor point mutant E4032A reveals an allosteric interaction with ryanodine.  Proc. Natl. Acad. Sci. U.S.A. 98 (2001) pp. 2865-2870.

Wang, Y., Fraefel, C., Protasi, F., Moore, R. A., Fessenden, J. D., Pessah, I. N., DiFrancesco, A., Breakefield, X., and Allen, P. D.  HSV-1 amplicon vectors are a highly efficient gene delivery system for skeletal muscle myoblasts and myotubes.  Am. J. Physiol. Cell Physiol.  278 (2000) pp. C619-C626.

Fessenden, J. D., Wang, Y., Moore, R. A., Chen, S. R. W., Allen, P. D. and Pessah, I. N.  Divergent functional properties of ryanodine receptor types 1 and 3 expressed in a myogenic cell line.  Biophys. J. 79 (2000) pp. 2509-2525.

PubMed:
Click here for a list of publications (searches the National Library of Medicine's PubMed database.)