Vivek Garg

Vivek Garg
University of Maryland, Baltimore | UMB · Department of Physiology

About

38
Publications
2,758
Reads
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533
Citations
Additional affiliations
June 2014 - June 2021
University of California, San Francisco
Position
  • Instructor
April 2009 - May 2014
University of Utah
Position
  • PostDoc Position
June 2004 - March 2009
The Ohio State University
Position
  • PhD Student

Publications

Publications (38)
Article
Full-text available
Ca2+ entry into mitochondria is through the mitochondrial calcium uniporter complex (MCUcx), a Ca2+-selective channel composed of five subunit types. Two MCUcx subunits (MCU and EMRE) span the inner mitochondrial membrane, while three Ca2+-regulatory subunits (MICU1, MICU2 and MICU3) reside in the intermembrane space. Here we provide rigorous analy...
Preprint
Mitochondrial Ca ²⁺ uniporter (MCU) mediates mitochondrial Ca ²⁺ uptake, regulating ATP production and cell death. According to the existing paradigm, MCU is occluded at the resting cytosolic [Ca ²⁺ ] and only opens above an ∼400 nM threshold. This Ca ²⁺ -dependent gating is putatively conferred by MICUs, EF hand-containing auxiliary subunits that...
Article
Calcium uptake by mitochondria plays an important role in sequestering cytosolic calcium, regulating ATP production and maintaining the redox homeostasis. Mitochondrial calcium uniporter (MCU), a macromolecular channel complex that resides in the inner mitochondrial membrane, is the primary electrogenic pathway for calcium influx into the matrix. B...
Chapter
Mitochondria accumulate significant amounts of calcium when cytosolic calcium is elevated above the resting levels of 50–100 nM during signaling events. This calcium uptake is primarily mediated by a macromolecular protein assembly called mitochondrial calcium uniporter (MCU) that resides in the mitochondrial inner membrane. In 2004, we applied pat...
Article
Life threatening ventricular arrhythmias leading to sudden cardiac death are a major cause of morbidity and mortality. In the absence of structural heart disease, these arrhythmias, especially in the younger population, are often an outcome of genetic defects in specialized membrane proteins called ion channels. In the heart, exceptionally well-orc...
Article
Full-text available
Calcium/calmodulin-dependent protein kinase II (CaMKII) regulates the principle ion channels mediating cardiac excitability and conduction, but how this regulation translates to the normal and ischemic heart remains unknown. Diverging results on CaMKII regulation of Na+ channels further prevent predicting how CaMKII activity regulates excitability...
Article
Full-text available
Global ischemia, catecholamine surge, and rapid heart rhythm (RHR) due to ventricular tachycardia or ventricular fibrillation (VF) are the three major factors of sudden cardiac arrest (SCA). Loss of excitability culminating in global electrical failure (asystole) is the major adverse outcome of SCA with increasing prevalence worldwide. The roles of...
Article
Mitochondrial membrane potential (ΔΨm) depolarization has been implicated in the loss of excitability (asystole) during global ischemia, which is relevant for the success of defibrillation and resuscitation after cardiac arrest. However, the relationship between ΔΨm depolarization and asystole during no-flow ischemia remains unknown. We applied spa...
Conference Paper
Myosin II inhibitor Blebbistatin is frequently used for heart immobilization during imaging experiments involving ischemia/reperfusion (I/R). Here we investigated the extent to which Blebbistatin modulates critical events during I/R, such as mitochondrial membrane potential depolarization (ΔΨm), asystole, and infarction. Langendorff-perfused rabbit...
Conference Paper
The critical events determining cell death in the aftermath of myocardial ischemia/reperfusion (I/R) remain poorly understood. Here we investigated the temporal relationship between the time of apparently complete mitochondrial inner membrane potential (ΔΨm) depolarization and the onset of sarcolemmal permeabilization (SP) during I/R using confocal...
Article
Full-text available
The activation gate of ion channels controls the transmembrane flux of permeant ions. In voltage-gated K(+) channels, the aperture formed by the S6 bundle crossing can widen to open or narrow to close the ion permeation pathway, whereas the selectivity filter gates ion flux in cyclic-nucleotide gated (CNG) and Slo1 channels. Here we explore the str...
Article
Full-text available
Ventricular fibrillation (VF) in the globally ischemic heart is characterized by a progressive electrical depression manifested as a decline in VF excitation rate (VFR) and loss of excitability, which occur first in the subepicardium (EPI) and spread to the subendocardium (ENDO). Early electrical failure is detrimental to successful defibrillation...
Article
The contribution of transient outward current (Ito) to changes in ventricular action potential (AP) repolarization induced by acidosis is unresolved as is the indirect effect of these changes on calcium handling. To address this issue we measured intracellular pH (pHi), Ito, L-type calcium current (ICa,L), and calcium transients (CaT) in rabbit ven...
Article
Full-text available
Rapid and voltage-dependent inactivation greatly attenuates outward currents in ether-a-go-go-related gene (ERG) K(+) channels. In contrast, inactivation of related ether-a-go-go (EAG) K(+) channels is very slow and minimally reduces outward currents. ICA-105574 (ICA, or 3-nitro-N-(4-phenoxyphenyl)-benzamide) has opposite effects on inactivation of...
Article
Full-text available
Ether-à-go-go (EAG) and EAG-related gene (ERG) K(+) channels are close homologues but differ markedly in their gating properties. ERG1 channels are characterized by rapid and extensive C-type inactivation, whereas mammalian EAG1 channels were previously considered noninactivating. Here, we show that human EAG1 channels exhibit an intrinsic voltage-...
Article
ICA activates hERG1 channels by reducing inactivation, but inhibits hEAG1 channels by inducing inactivation. Molecular modeling suggests that ICA binds to a pocket located between S5 and S6 in both channels. A mutation in S5 (F557L) or S6 (Y652A) of hERG1 eliminates the activity of ICA, indicating a key role of these residues in the drug binding si...
Article
Ether-a-go-go (EAG) family potassium channels, including hEAG1 and hERG1 play an important role in the heart, CNS, cell cycle regulation and cancer. ICA-105574 (ICA) was previously reported to activate hERG1 current by causing a large depolarizing shift in the V0.5 for P-type inactivation (Gerlach et al, Mol. Pharmacol. 2010, 77: 58). The related h...
Article
Full-text available
Human ether-à-go-go-related gene 1 (hERG1) channels mediate repolarization of cardiac action potentials. Inherited long QT syndrome (LQTS) caused by loss-of-function mutations, or unintended blockade of hERG1 channels by many drugs, can lead to severe arrhythmia and sudden death. Drugs that activate hERG1 are a novel pharmacological approach to tre...
Article
Full-text available
Slo2.1 channels conduct an outwardly rectifying K(+) current when activated by high [Na(+)](i). Here, we show that gating of these channels can also be activated by fenamates such as niflumic acid (NFA), even in the absence of intracellular Na(+). In Xenopus oocytes injected with <10 ng cRNA, heterologously expressed human Slo2.1 current was neglig...
Article
Full-text available
Increased O(2)(*-) and NO production is a key mechanism of mitochondrial dysfunction in myocardial ischemia/reperfusion injury. In complex II, oxidative impairment and enhanced tyrosine nitration of the 70 kDa FAD-binding protein occur in the post-ischemic myocardium and are thought to be mediated by peroxynitrite (OONO(-)) in vivo [Chen, Y.-R., et...
Article
We have recently shown that ATP-sensitive potassium (K(ATP)) channels in the heart are localized in the caveolae of cardiac myocytes and regulated by caveolae-related signaling. However, little is known about the role of caveolins, signature proteins of caveolae, in cardiac K(ATP) channel function. The present study was designed to explore the pote...
Article
ATP-sensitive potassium (K(ATP)) channels in the heart are critical regulators of cellular excitability and action potentials during ischaemia. However, little is known about subcellular localization of these channels and their regulation. The present study was designed to explore the potential role of caveolae in the regulation of K(ATP) channels...
Article
Vascular ATP-sensitive K(+) (K(ATP)) channels are critical regulators of arterial tone and, thus, blood flow in response to local metabolic needs. They are important targets for clinically used drugs to treat hypertensive emergency and angina. It is known that protein kinase C (PKC) activation inhibits K(ATP) channels in vascular smooth muscles. Ho...
Article
Full-text available
ATP-sensitive K+ (K ATP) channels are implicated in the protective effect of ischaemic preconditioning (IPC). Kir6.2 has been shown to be involved in the cardioprotection of IPC. However, the mechanism by which Kir6.2-containing K ATP channels protect the heart is still largely unknown. The present study was designed to explore the potential mechan...
Article
Vascular ATP-sensitive K ⁺ (K ATP ) channels are critical regulators of arterial tone, thus blood flow in response to local metabolic needs. They are important targets for clinically used drugs to treat hypertensive emergency and angina. It is well known that protein kinase C (PKC) activation inhibits K ATP channels in vascular smooth muscles. Howe...
Article
The ATP-sensitive K(+) (K(ATP)) channels in both sarcolemmal (sarcK(ATP)) and mitochondrial inner membrane (mitoK(ATP)) are the critical mediators in cellular protection of ischemic preconditioning (IPC). Whereas cardiac sarcK(ATP) contains Kir6.2 and sulfonylurea receptor (SUR)2A, the molecular identity of mitoK(ATP) remains elusive. In the presen...
Article
The present study was carried out using mice model of chronic fatigue syndrome (CFS) in which mice were forced to swim everyday for 7 days for a 6 min session. There was a significant increase in despair behavior (immobility period) in saline treated mice on successive days. Treatment with potent antioxidants carvedilol (5 mg/kg, i.p.) and melatoni...

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