Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.
Circulation: Arrhythmia and Electrophysiology 9(5) (2016)
Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyze...
Mechanisms of Calmodulin Regulation of Different Isoforms of Kv7.4 K+ Channels.
Journal of Biological Chemistry 291(5):2499 (2016)
Calmodulin (CaM), a Ca(2+)-sensing protein, is constitutively bound to IQ domains of the C termini of human Kv7 (hKv7, KCNQ) channels to mediate Ca(2+)-dependent reduction of Kv7 currents. However, the mechanism remains unclear. We report that CaM binds to two isoforms of the hKv7.4 channel in a...
Multimodal SHG-2PF Imaging of Microdomain Ca2+-Contraction Coupling in Live Cardiac Myocytes.
Circulation Research 118(2):e19 (2016)
Cardiac myocyte contraction is caused by Ca(2+) binding to troponin C, which triggers the cross-bridge power stroke and myofilament sliding in sarcomeres. Synchronized Ca(2+) release causes whole cell contraction and is readily observable with current microscopy techniques. However, it is unknow...
In Vivo Cannulation Methods for Cardiomyocytes Isolation from Heart Disease Models.
PLoS ONE 11(8):e0160605 (2016)
Isolation of high quality cardiomyocytes is critically important for achieving successful experiments in many cellular and molecular cardiology studies. Methods for isolating cardiomyocytes from the murine heart generally are time-sensitive and experience-dependent, and often fail to produce hig...
Aerobic exercise-based rehabilitation affects the activities of progenitor endothelial cells through EETs pathway.
Medical Hypotheses 85(6):1037 (2015)
Feedback mechanisms for cardiac-specific microRNAs and cAMP signaling in electrical remodeling.
Circulation: Arrhythmia and Electrophysiology 8(4):942 (2015)
Loss of transient outward K(+) current (Ito) is well documented in cardiac hypertrophy and failure both in animal models and in humans. Electrical remodeling contributes to prolonged action potential duration and increased incidence of arrhythmias. Furthermore, there is a growing body of evidenc...
Small-conductance Ca2+ -activated K+ channels and cardiac arrhythmias.
Heart Rhythm 12(8):1845 (2015)
Small-conductance Ca2+ -activated K+ (SK, KCa2) channels are unique in that they are gated solely by changes in intracellular Ca2+ and, hence, function to integrate intracellular Ca2+ and membrane potentials on a beat-to-beat basis. Recent studies have provided evidence for the existence and fun...
Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice.
Toxicology and Applied Pharmacology 286(2):102 (2015)
Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, panc...
Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis.
Atherosclerosis 239(2):557 (2015)
Adipose tissue is the body largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), which maintains plasma high-density lipoprotein (HDL) levels. HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Solub...
Na+ channel function, regulation, structure, trafficking and sequestration.
Journal of Physiology 593(6):1347 (2015)
This paper is the second of a series of three reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation-contraction coupling and arrhythmias: Na(+) channel and Na(+) transport. The goal of...
Identification of a key residue in Kv7.1 potassium channel essential for sensing external potassium ions.
Journal of General Physiology 145(3):201 (2015)
Kv7.1 voltage-gated K(+) (Kv) channels are present in the apical membranes of marginal cells of the stria vascularis of the inner ear, where they mediate K(+) efflux into the scala media (cochlear duct) of the cochlea. As such, they are exposed to the K(+)-rich (∼ 150 mM of external K(+) (K(+) e...
Etiology of distinct membrane excitability in pre- and posthearing auditory neurons relies on activity of Cl- channel TMEM16A.
PNAS 112(8):2575 (2015)
The developmental rehearsal for the debut of hearing is marked by massive changes in the membrane properties of hair cells (HCs) and spiral ganglion neurons (SGNs). Whereas the underlying mechanisms for the developing HC transition to mature stage are understood in detail, the maturation of SGNs...
Regulation of gene transcription by voltage-gated L-type calcium channel, Cav1.3.
Journal of Biological Chemistry 290(8):4663 (2015)
Cav1.3 L-type Ca(2+) channel is known to be highly expressed in neurons and neuroendocrine cells. However, we have previously demonstrated that the Cav1.3 channel is also expressed in atria and pacemaking cells in the heart. The significance of the tissue-specific expression of the channel is un...
Progress toward the prevention and treatment of atrial fibrillation: A summary of the Heart Rhythm Society Research Forum on the Treatment and Prevention of Atrial Fibrillation, Washington, DC, December 9-10, 2013.
Heart Rhythm 12(1):e5 (2015)
Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel.
PNAS 111(27):9989 (2014)
For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effect...
Genetic, cellular, and functional evidence for Ca2+ inflow through Cav1.2 and Cav1.3 channels in murine spiral ganglion neurons.
Journal of Neuroscience 34(21):7383 (2014)
Spiral ganglion neurons (SGNs) of the eighth nerve serve as the bridge between hair cells and the cochlear nucleus. Hair cells use Cav1.3 as the primary channel for Ca(2+) inflow to mediate transmitter release. In contrast, SGNs are equipped with multiple Ca(2+) channels to mediate Ca(2+)-depend...
Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling.
Science Signaling 7(317):ra27 (2014)
Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanica...
Critical roles of a small conductance Ca²⁺-activated K⁺ channel (SK3) in the repolarization process of atrial myocytes.
Cardiovascular Research 101(2):317 (2014)
Small conductance Ca(2+)-activated K(+) channels (K(Ca)2 or SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(i)²⁺) with membrane potentials. We have recently reported the functional expression of SK channels in human and mouse ...
Localized Nitric Oxide Signaling Mediates Cardiac Mechano-Chemotransduction
Biophysical Journal 106(2):566a (2014)
A-Actinin2 and Filamin a Cytoskeletal Interacting Proteins Facilitate SK2 Channels Recycling from Endosomes to the Surface Membrane
Biophysical Journal 106(2):118a (2014)