
Riccardo Olcese
Professor, Anesthesiology, University of California Los Angeles
Professor, Physiology, University of California Los Angeles
rolcese@ucla.edu
310-206-2214
Office Address:
100 Jules Stein Plaza
Division of Molecular Medicine
Dept. of Anesthesiology and Perioperative Medicine
Los Angeles, CA 90095
Work Address:
CHS
Los Angeles, CA 90095
Lab Number:
310-206-2685
Affiliations
Member, Molecular Medicine, Biochemistry, Biophysics & Structural Biology GPB Home Area, Brain Research Institute, Molecular, Cellular & Integrative Physiology GPB Home Area, Neuroscience GPB Home Area
Faculty, Cardiovascular Research Laboratory
Faculty, Cardiovascular Research Laboratory
Research Interests
The general aim of my research is to define the role of ion channels in the control and regulation of cell excitability. Ion channels are membrane proteins that regulate the flow of ions across the cell membrane that in turn control a variety of functions such as neuronal excitability, heartbeat, muscle contraction and hormones release. Ion channels are transmembrane proteins usually associated with accessory subunits that modulate their function. The regulation mechanism(s) of voltage dependent channel activity by accessory subunits and second messengers is one of my strongest interests. In these studies, by combining state-of-the-art electrophysiological techniques (cut-open oocyte voltage clamp, patch clamp, macropatch) with mutagenesis, we identifying the structural determinants for the various channel functions (activation, inactivation, conduction and sensitivity to drugs). STRUCTUTRAL REARRANGEMENTS OF CHANNEL PROTEINS DURING GATING Voltage-dependent ion channels respond to changes of membrane potential by a rearrangement of a voltage sensing structure. The movement of the voltage sensor produces a conformational change of the channel that allows ion conduction through the pore. Part of my research is currently dedicated to understand the coupling mechanism between the movements of the voltage sensor and pore opening. This study involves the measurement of small currents (gating currents) generated by the movement of the charged voltage sensor across the transmembrane electric field. Gating currents reveal the conformational changes of the channel protein, occurring before and during channel opening. In this research program, we combine optical methods with classical electrophysiology to detect conformational changes of the channels. This novel approach in ion channels studies allows detecting conformational changes of channel protein as changes in fluorescence properties of fluorophores covalently attached to selected positions on the protein (voltage clamp + site directed fluorescence labeling). One of the goals is to correlate at the molecular level the structural changes of the channel protein with the different phases of channel activity. At this moment, I am using this approach to investigate the properties of voltage and calcium activated (BK) channels. The final objective is to obtain a molecular and dynamic view of BK channels by identifying the mobile regions underlying voltage sensing. MECHANISMS OF ION PERMEATION THROUGH ION CHANNEL: We are currently investigating how the amino acids in close proximity of the conduction pore are affecting the conduction properties of voltage- and calcium-activated K+ channels. In combination with theoretical, biophysical and pharmacological studies, we learn about the basic mechanism of ion permeation and channel gating at the molecular level. One of the objectives is to understand the unique permeation properties of BK channels, which allow K+ to permeate 20fold better in respect to other potassium channels that share very similar amino acid pore sequences. CARDIAC ARRHYTHMIAS AND FIBRILLATION In collaboration with Dr J. Weiss, we are developing a research program focused cardiac arrhythmias and fibrillation. Activation and inactivation of voltage dependent calcium channels play a key role in the stability of the cardiac rhythm, through their effects on action potential properties. The goal is to is to control cardiac excitability, by fine tuning the the activity of cardiac L-type calcium channels using their own modulatory subunits. The project should set basis for a larger gene-therapy related project
Publications
- Qu Z, Liu MB, Olcese R, Karagueuzian H, Garfinkel A, Chen PS, Weiss JN. R-on-T and the Initiation of Reentry Revisited: Integrating Old and New Concepts.. Heart rhythm, 2022.
- Angelini M, Pezhouman A, Savalli N, Chang MG, Steccanella F, Scranton K, Calmettes G, Ottolia M, Pantazis A, Karagueuzian HS, Weiss JN, Olcese R. Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current.. The Journal of general physiology, 2021.
- Savalli N, Angelini M, Steccanella F, Wier J, Wu F, Quinonez M, DiFranco M, Neely A, Cannon SC, Olcese R. The distinct role of the four voltage sensors of the skeletal CaV1.1 channel in voltage-dependent activation.. The Journal of general physiology, 2021.
- Zyrianova T, Lopez B, Liao A, Gu C, Wong L, Ottolia M, Olcese R, Schwingshackl A. BK Channels Regulate LPS-induced CCL-2 Release from Human Pulmonary Endothelial Cells.. American journal of respiratory cell and molecular biology, 2021.
- Zyrianova T, Lopez B, Olcese R, Belperio J, Waters CM, Wong L, Nguyen V, Talapaneni S, Schwingshackl A. K2P2.1 (TREK-1) potassium channel activation protects against hyperoxia-induced lung injury.. Scientific reports, 2020.
- Pantazis A, Kaneko M, Angelini M, Steccanella F, Westerlund AM, Lindström SH, Nilsson M, Delemotte L, Saitta SC, Olcese R. Tracking the motion of the KV 1.2 voltage sensor reveals the molecular perturbations caused by a de novo mutation in a case of epilepsy.. The Journal of physiology, 2020.
- Landaw J, Zhang Z, Song Z, Liu MB, Olcese R, Chen PS, Weiss JN, Qu Z. Small-conductance Ca2+-activated K+ channels promote J-wave syndrome and phase 2 reentry.. Heart rhythm, 2020.
- Seki S, Yamamoto T, Quinn K, Spigelman I, Pantazis A, Olcese R, Wiedau-Pazos M, Chandler SH, Venugopal S. Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1G93A Mouse Model for ALS.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019.
- Balderas E, Torres NS, Rosa-Garrido M, Chaudhuri D, Toro L, Stefani E, Olcese R. MitoBKCa channel is functionally associated with its regulatory β1 subunit in cardiac mitochondria.. The Journal of physiology, 2019.
- Venugopal S, Seki S, Terman DH, Pantazis A, Olcese R, Wiedau-Pazos M, Chandler SH. Resurgent Na+ Current Offers Noise Modulation in Bursting Neurons.. PLoS computational biology, 2019.
- Pantazis A, Westerberg K, Althoff T, Abramson J, Olcese R. Harnessing photoinduced electron transfer to optically determine protein sub-nanoscale atomic distances.. Nature communications, 2018.
- John S, Kim B, Olcese R, Goldhaber JI, Ottolia M. Molecular determinants of pH regulation in the cardiac Na+-Ca2+ exchanger.. The Journal of general physiology, 2018.
- Schwingshackl A, Lopez B, Teng B, Luellen C, Lesage F, Belperio J, Olcese R, Waters CM. Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins.. American journal of physiology. Lung cellular and molecular physiology, 2017.
- Karagueuzian HS, Pezhouman A, Angelini M, Olcese R. Enhanced Late Na and Ca Currents as Effective Antiarrhythmic Drug Targets.. Frontiers in pharmacology, 2017.
- Zhang J, Li M, Zhang Z, Zhu R, Olcese R, Stefani E, Toro L. The mitochondrial BKCa channel cardiac interactome reveals BKCa association with the mitochondrial import receptor subunit Tom22, and the adenine nucleotide translocator.. Mitochondrion, 2016.
- Savalli N, Pantazis A, Sigg D, Weiss JN, Neely A, Olcese R. The α2δ-1 subunit remodels CaV1.2 voltage sensors and allows Ca2+ influx at physiological membrane potentials.. The Journal of general physiology, 2016.
- Prudat Y, Madhvani RV, Angelini M, Borgstom NP, Garfinkel A, Karagueuzian HS, Weiss JN, de Lange E, Olcese R, Kucera JP. Stochastic pacing reveals the propensity to cardiac action potential alternans and uncovers its underlying dynamics.. The Journal of physiology, 2016.
- Madhvani RV, Angelini M, Xie Y, Pantazis A, Suriany S, Borgstrom NP, Garfinkel A, Qu Z, Weiss JN, Olcese R. Targeting the late component of the cardiac L-type Ca2+ current to suppress early afterdepolarizations.. The Journal of general physiology, 2015.
- Weiss JN, Garfinkel A, Karagueuzian HS, Nguyen TP, Olcese R, Chen PS, Qu Z. Perspective: a dynamics-based classification of ventricular arrhythmias.. Journal of molecular and cellular cardiology, 2015.
- Pantazis A, Savalli N, Sigg D, Neely A, Olcese R. Functional heterogeneity of the four voltage sensors of a human L-type calcium channel.. Proceedings of the National Academy of Sciences of the United States of America, 2014.
- Qu Z, Xie LH, Olcese R, Karagueuzian HS, Chen PS, Garfinkel A, Weiss JN. Early afterdepolarizations in cardiac myocytes: beyond reduced repolarization reserve.. Cardiovascular research, 2013.
- Pantazis A, Olcese R. Relative transmembrane segment rearrangements during BK channel activation resolved by structurally assigned fluorophore-quencher pairing.. The Journal of general physiology, 2012.
- Savalli N, Pantazis A, Yusifov T, Sigg D, Olcese R. The contribution of RCK domains to human BK channel allosteric activation.. The Journal of biological chemistry, 2012.
- Madhvani RV, Xie Y, Pantazis A, Garfinkel A, Qu Z, Weiss JN, Olcese R. Shaping a new Ca²⁺ conductance to suppress early afterdepolarizations in cardiac myocytes.. The Journal of physiology, 2011.
- Olcese R. I(KACh) at the whim of a capricious M2R.. The Journal of physiology, 2011.
- Javaherian AD, Yusifov T, Pantazis A, Franklin S, Gandhi CS, Olcese R. Metal-driven operation of the human large-conductance voltage- and Ca2+-dependent potassium channel (BK) gating ring apparatus.. The Journal of biological chemistry, 2011.
- Pantazis A, Kohanteb AP, Olcese R. Relative motion of transmembrane segments S0 and S4 during voltage sensor activation in the human BK(Ca) channel.. The Journal of general physiology, 2010.
- Yusifov T, Javaherian AD, Pantazis A, Gandhi CS, Olcese R. The RCK1 domain of the human BKCa channel transduces Ca2+ binding into structural rearrangements.. The Journal of general physiology, 2010.
- Pantazis A, Gudzenko V, Savalli N, Sigg D, Olcese R. Operation of the voltage sensor of a human voltage- and Ca2+-activated K+ channel.. Proceedings of the National Academy of Sciences of the United States of America, 2010.
- Olcese R. It's spring-time for slow inactivation.. The Journal of general physiology, 2009.
- Mahajan A, Shiferaw Y, Sato D, Baher A, Olcese R, Xie LH, Yang MJ, Chen PS, Restrepo JG, Karma A, Garfinkel A, Qu Z, Weiss JN. A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.. Biophysical journal, 2008.
- Mahajan A, Sato D, Shiferaw Y, Baher A, Xie LH, Peralta R, Olcese R, Garfinkel A, Qu Z, Weiss JN. Modifying L-type calcium current kinetics: consequences for cardiac excitation and arrhythmia dynamics.. Biophysical journal, 2008.
- Gandhi CS, Olcese R. The voltage-clamp fluorometry technique.. Methods in molecular biology (Clifton, N.J.), 2008.
- Yusifov T, Savalli N, Gandhi CS, Ottolia M, Olcese R. The RCK2 domain of the human BKCa channel is a calcium sensor.. Proceedings of the National Academy of Sciences of the United States of America, 2007.
- Savalli N, Kondratiev A, de Quintana SB, Toro L, Olcese R. Modes of operation of the BKCa channel beta2 subunit.. The Journal of general physiology, 2007.
- Olcese R. And yet it moves: conformational States of the Ca2+ channel pore.. The Journal of general physiology, 2007.
- Gudzenko V, Shiferaw Y, Savalli N, Vyas R, Weiss JN, Olcese R. Influence of channel subunit composition on L-type Ca2+ current kinetics and cardiac wave stability.. American journal of physiology. Heart and circulatory physiology, 2007.
- Savalli N, Kondratiev A, Toro L, Olcese R. Voltage-dependent conformational changes in human Ca(2+)- and voltage-activated K(+) channel, revealed by voltage-clamp fluorometry.. Proceedings of the National Academy of Sciences of the United States of America, 2006.
- Chen ZW, Chang CS, Leil TA, Olcese R, Olsen RW. GABAA receptor-associated protein regulates GABAA receptor cell-surface number in Xenopus laevis oocytes.. Molecular pharmacology, 2005.
- Haug T, Sigg D, Ciani S, Toro L, Stefani E, Olcese R. Regulation of K+ flow by a ring of negative charges in the outer pore of BKCa channels. Part I: Aspartate 292 modulates K+ conduction by external surface charge effect.. The Journal of general physiology, 2004.
- Haug T, Olcese R, Toro L, Stefani E. Regulation of K+ flow by a ring of negative charges in the outer pore of BKCa channels. Part II: Neutralization of aspartate 292 reduces long channel openings and gating current slow component.. The Journal of general physiology, 2004.
- Latorre R, Olcese R, Basso C, Gonzalez C, Munoz F, Cosmelli D, Alvarez O. Molecular coupling between voltage sensor and pore opening in the Arabidopsis inward rectifier K+ channel KAT1.. The Journal of general physiology, 2003.
- Chang CS, Olcese R, Olsen RW. A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation.. The Journal of biological chemistry, 2003.
- Helguera G, Olcese R, Song M, Toro L, Stefani E. Tissue-specific regulation of Ca(2+) channel protein expression by sex hormones.. Biochimica et biophysica acta, 2002.