SEMINAR: Regulation of the L-type Ca2+ channel by free radicals and role in the development of cardiac hypertrophy
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Regulation of the L-type Ca2+ channel by free radicals and role in the development of cardiac hypertrophy : School of Anatomy & Human Biology Seminar Series |
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The Seminar: The L-type Ca2+ channel plays a critical role in cardiac excitation and contraction and it is the main route for calcium influx into cardiac myocytes. The function of the channel can be modified during alterations in cellular redox state. A reduced cellular state such as during acute hypoxia can alter the basal channel activity and the sensitivity of the channel to beta-adrenergic receptor activation. Thiol reducing agents mimic the effect of hypoxia suggesting an involvement of cysteines on the channel protein or a regulatory protein. We have experimental evidence this can lead to altered cellular excitation, induction of early afterdepolarizations and arrhythmia. Conversely we have found that an increase in cellular oxidative stress can increase channel activity and persistently alter cellular calcium homeostasis. This leads to in an increase in cellular protein synthesis consistent with the development of hypertrophy. We are now interested in determining how the channel protein is altered during changes in the cell’s redox state and present evidence for direct glutathionylation of the channel protein during increases in oxidative stress including ischemia reperfusion injury.
The Speaker: Livia Hool completed her PhD in cellular electrophysiology at Royal North Shore Hospital, Sydney in 1995. She then undertook 2 years postdoctoral research as recipient of an American Heart Association Postdoctoral Fellowship in the School of Medicine, Case Western Reserve University, Cleveland, Ohio. In 1998 she was awarded a Peter Doherty Fellowship from NHMRC and relocated to the University of Western Australia where she established the Cardiovascular Electrophysiology Laboratory in the Physiology Department, UWA. Her research interests include understanding the regulation of cardiac ion channels under pathologically relevant conditions such as hypoxia and oxidative stress including redox modification of the channel protein. She is currently recipient of an ARC Future Fellowship and Honorary NHMRC Senior Research Fellowship.
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