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UCLA Cardiovascular Research Theme

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UCLA Cardiovascular Research Theme

Riccardo Olcese, PhD

Riccardo Olcese, PhD 
Email: rolcese@ucla.edu

Ion Channels · Cardiac Arrhythmia · Early Afterdepolarizations (EAD)

Ion channelsand their role in cellular excitability are central themes of the research programs developed in the laboratoryof Dr. Riccardo Olcese at UCLA, which integrates molecular-level biophysical studies with organ-wide phenomena of clinical significance, such as cardiac arrhythmia. The quantitative tools of biophysics are used in a translational context to understandthe role of ion channels in health and disease.

Every year in the United States >300,000 people suffer a sudden cardiac death, due to ventricular arrhythmias. We are investigating the arrhythmogenic properties of anomalies of the repolarization phase of the cardiac action potential known as Early Afterdepolarizations (EAD). We are searching for novel interventions to prevent EADs and their arrhythmogenic consequences by modulating the activity of cardiac L-type calcium channelswithout adverse effects on contractility (excitation-contraction coupling). The laboratory also explores the fundamental mechanisms of ion channel function. Ion channelsare exquisitely complex membrane proteins that control specific ionic fluxes across the cell membranecontrolling cell excitability.

We learn about the molecular and structural basis of ion channelfunctionand regulation in theheart, muscleand nerves.We are particularly interested in voltage-activated channels, which respond to changes in the membrane potential with a rearrangement of their voltage sensing structures. We study how their voltage sensing structures operatedriving the channel into ion-conducting (open) and closed conformations. We use state-of-the-art techniques in electrophysiology, biochemistry, molecular biology, computational modeling.By combining optical methods with electrophysiology,we track in real time the structural changes of ion channel associated with their operation(Voltage-Clamp Fluorometry).

Other independent laboratories associated with ion channel research include Dr. Cannon, Dr Qu, Dr Garfinkel and Dr Scott John (pls see individual lab profiles)

Publications

  • Madhvani, R. V., Angelini, M., Xie, Y., Pantazis, A., Suriany, S., Borgstrom, N. P., Garfinkel, A., Qu, Z., Weiss, J. N., & Olcese, R. (2015). Targeting the late component of the cardiac L-type Ca2+ current to suppress early afterdepolarizations.The Journal of general physiology,145(5), 395–404. https://doi.org/10.1085/jgp.201411288
  • Antonios Pantazis, Karin Westerberg, Thorsten Althoff, Jeff Abramson, Riccardo Olcese (2018)Harnessing photoinduced electron transfer to optically determine protein sub-nanoscale atomic distances. Nature Communications https://dx.doi.org/10.1038/s41467-018-07218-6
  • Pantazis A, Savalli N, Sigg D, Neely A, Olcese R. (2014) Functional heterogeneity of the four voltage sensors of a human L-type calcium channel. Proc Natl Acad Sci U S Ahttps://doi.org/10.1073/pnas.1411127112

Full PubMed Bibliography

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