Alexey Glukhov, PhD

Research Interests

Our laboratory is a part of the Cellular and Molecular Arrhythmia Research Program (CMARP) involving multiple investigators working on a wide range of research projects exploring the molecular function of ion channels in human physiology, pharmacology, and disease. Our research interests are focused on studying cellular and molecular mechanisms of cardiac excitability and contractility, neurohormonal regulation of cardiac physiology, and mechanisms of abnormal heart rhythms (arrhythmias). We use electrophysiology, cell biology, molecular biology techniques, and various state-of-the art imaging modalities to identify triggers and treatments of cardiac disease. The primary goal of our research is to improve the health of people with cardiac arrhythmias, including the most common abnormal heart rhythm, atrial fibrillation, affecting about 2% to 3% of the Western population. To accomplish this, we aim to identify novel diagnostic tools and therapeutic targets through investigation of mechanisms of cardiac remodeling and arrhythmogenesis.

Our group has a multidisciplinary background that includes expertise in physiology, cell biology, biomedical engineering, biophysics, and confocal microscopy. We employ several state-of-the-art techniques, including high-resolution fluorescent optical mapping and scanning ion conductance microscopy (SICM) equipped with “smart” patch-clamp. This unique set of skills and experimental techniques allow us to investigate mechanisms of arrhythmias across multiple scales from protein expression, localization and function, to electrical and mechanical activity of an intact heart. Our research is specifically focused on elucidating the functionality of subcellular nanodomains and their role in regulation of proteins responsible for normal and pathophysiological electro-mechanical activity of the heart. We pursue two main directions: (1) determining the cellular and molecular mechanisms underlying normal electrical activity and dysfunction of the sinoatrial node, the heart’s natural pacemaker, and (2) discovering novel strategies for atrial fibrillation treatment and risk stratification.

Selected Publications

Lang D, Medvedev R, Ratajczyk L, Zheng Z, Yuan X, Lim E, Han OY, Valdivia HH, Glukhov AV. Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atria. Am J Physiol Heart Circ Physiol. 2022; 322(2):H269-H284.

Turner D, Kang C, Mesirca P, Hong J, Mangoni ME, Glukhov AV, Sah R. Electrophysiological and Molecular Mechanisms of Sinoatrial Node Mechanosensitivity. Front Cardiovasc Med. 2021; 8:662410.

Lang D, Glukhov AV. Cellular and molecular mechanisms of functional hierarchy of pacemaker clusters in the sinoatrial node: New insights into sick sinus syndrome. J Cardiovasc Dev Dis. 2021, 8(4), 43.

De Lange W, Farrell E, Kreitzer C, Jacobs D, Lang D, Glukhov AV, Ralphe J. Human iPSC engineered cardiac tissue platform faithfully models important cardiac physiology. Am J Physiol Heart Circ Physiol. 2021; 320(4):H1670-H1686.

Medvedev RY, Sanchez-Alonso JL, Mansfield CA, Judina A, Francis AJ, Pagiatakis C, Trayanova N, Glukhov AV, Miragoli M, Faggian G, Gorelik J. Local hyperactivation of L-type Ca²⁺ channels, increases spontaneous Ca²⁺ release activity and cellular hypertrophy in right ventricular myocytes from heart failure rats. Sci Rep. 2021; 11(1):4840.

Tyan L, Turner D, Komp KR, Medvedev R, Lim E, Glukhov AV. Caveolin-3 is required for regulation of transient outward potassium current by angiotensin II in mouse atrial myocytes. Am J Physiol Heart Circ Physiol. 2021; 320(2): H787-H797.

Napiwocki BN, Lang D, Stempien A, Zhang J, Vaidyanathan R, Makielski JC, Eckhardt LL, Glukhov AV, Kamp TJ, Crone WC. Aligned Human Cardiac Syncytium for In Vitro Analysis of Electrical, Structural and Mechanical Readouts. Biotechnology and Bioengineering. 2021; 118(1): 442-452.

Reilly L, Alvarado FJ, Lang D, Abozeid S, Van Ert H, Spellman C, Warden J, Makielski JC, Glukhov AV, Eckhardt LL. Phase 3 early afterdepolarizations underlie the ventricular arrhythmic mechanism from a KCNJ2 mutation in vivo model. Circ Arrhythm Electrophysiol. 2020; 13(9):e008638.

Egorov YV, Rosenshtraukh LV, Glukhov AV. Arrhythmogenic interaction between sympathetic tone and mechanical stretch in rat pulmonary vein myocardium. Front. Physiol. 2020; 11:237.

Egorov YV, Lang D, Tyan L, Turner D, Lim E, Piro ZD, Hernandez JJ, Lodin R, Wang R, Schmuck EG, Raval AN, Ralphe CJ, Kamp TJ, Rosenshtraukh LV, Glukhov AV. Caveolae-Mediated Activation of Mechanosensitive Chloride Channels Triggers Atrial Arrhythmogenesis. J Am Heart Assoc. 2019; 8(20): e012748.

Lang D, Glukhov AV. Functional Microdomains in Heart’s Pacemaker: A Step Beyond Classical Electrophysiology and Remodeling. Front Physiol. 2018; 9:1686.

Lang D, Glukhov AV. High-resolution optical mapping of the mouse sino-atrial node. Journal of Visualized Experiments. 2016; (118): 54773.

Glukhov AV, Balycheva M, Sanchez-Alonso JS, Ilkan Z, Alvarez Laviada A, Bhogal N, Diakonov I, Schobesberger S, Bhargava A, Faggian G, Houser SR, Gorelik J. Direct evidence for microdomain-specific localization and remodeling of functional L-type calcium channels in rat and human atrial myocytes. Circulation. 2015; 132(25): 2372-84.

Complete list of publications (GoogleScholar)