Show simple item record

dc.contributor.authorBalog, Edward M.
dc.date.accessioned2013-07-12T13:41:51Z
dc.date.available2013-07-12T13:41:51Z
dc.date.issued2013-07-09
dc.identifier.urihttp://hdl.handle.net/1853/48351
dc.descriptionPresented on July 9, 2013 from 8:30 a.m.-9:30 a.m. at the Parker H. Petit Institute for Bioengineering & Bioscience (IBB), room 1128, Georgia Tech.en_US
dc.descriptionEdward M. Balog is an Associate Professor in the School of Applied Physiology, Georgia Institute of Technology.
dc.descriptionRuntime: 62:27 minutes
dc.description.abstractFluctuations in the intracellular calcium (Ca2+) concentration are used to signal numerous cellular events. Impaired cellular Ca2+ regulation can lead to pathology and cell death, thus tight control of intracellular Ca2+ concentration is vital to the survival of all cells. This a particular challenge for cardiac and skeletal muscle cells as they use the controlled release of Ca2+ from the sarcoplasmic reticulum (SR) to initiate skeletal muscle contraction and the heartbeat. Ryanodine receptor (RyR) Ca2+ channels are the efflux pathway for the release of Ca2+ from the SR, however, these channels are not simple conduits for calcium efflux; rather they integrate cellular signals to finely tune Ca2+ release from intracellular stores. The critical role these channels play in muscle function is exemplified by the mutations in the channels that can lead to lethal cardiac arrhythmia or adverse reactions to anesthetics. Further these channel may contribute to muscle weakness associated with skeletal muscle fatigue and aging. A thorough understanding of RyR channel regulation by endogenous effectors is not only critical for our understanding of muscle function but may contribute to the development of therapeutic agents targeting these channels. I will discuss our work on two potential endogenous channel regulators, S-adenosyl-l-methionine (SAM) and calmodulin (CaM) and briefly describe some of our aging work. Physiological concentrations of SAM, the primary methyl group donor for enzyme-mediated methylation, activated the cardiac isoform of the RyR. This effect of SAM was unrelated to its role as a methyl group donor but rather was mediated by a RyR adenine nucleotide-binding site. Interestingly, SAM but not ATP activation was associated with a marked increase in the frequency of channel openings to a sub-conductance level. CaM is a small, ubiquitous protein that contains Ca2+-binding sites in each of its two lobes. Ca2+-free CaM activates the skeletal muscle RyR and Ca2+-bound CaM inhibits the channel. We have identified a CaM Ca2+-binding site required for the conversion of CaM from a RyR activator to a channel inhibitor. By manipulating the Ca2+ affinity of this site, we were able to modify the RyR activation profile. Future goals include defining the molecular characteristics required for adenine nucleotide activation of RyR channels and determining the role of CaM in voltage-activation of skeletal muscle.en_US
dc.format.extent62:27 minutes
dc.language.isoen_USen_US
dc.publisherGeorgia Institute of Technologyen_US
dc.relation.ispartofseriesPetit Institute Breakfast Club Seminar Series
dc.subjectExcitation-contraction couplingen_US
dc.subjectMuscle contractionen_US
dc.subjectRyanodineen_US
dc.subjectSarcoplasmic reticulumen_US
dc.titleRegulation of Ryanodine Receptor Calcium Release Channels by Endogenous Effectorsen_US
dc.typeLectureen_US
dc.typeVideoen_US
dc.contributor.corporatenameGeorgia Institute of Technology. Institute for Bioengineering and Bioscienceen_US
dc.contributor.corporatenameGeorgia Institute of Technology. School of Applied Physiologyen_US
dc.embargo.termsnullen_US


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record