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...
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...
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...
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 ...
Critical Roles of SK3 Calcium-Activated Potassium Channels in the Repolarization of Atrial Myocytes
Biophysical Journal 106(2):118a (2014)
Adenylyl cyclase subtype-specific compartmentalization: differential regulation of L-type Ca2+ current in ventricular myocytes.
Circulation Research 112(12):1567 (2013)
Adenylyl cyclase (AC) represents one of the principal molecules in the β-adrenergic receptor signaling pathway, responsible for the conversion of ATP to the second messenger, cAMP. AC types 5 (ACV) and 6 (ACVI) are the 2 main isoforms in the heart. Although highly homologous in sequence, these 2...
Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle.
PNAS 109(35):14158 (2012)
Triclosan (TCS), a high-production-volume chemical used as a bactericide in personal care products, is a priority pollutant of growing concern to human and environmental health. TCS is capable of altering the activity of type 1 ryanodine receptor (RyR1), but its potential to influence physiologi...
MicroRNA profiling predicts a variance in the proliferative potential of cardiac progenitor cells derived from neonatal and adult murine hearts.
Journal of Molecular and Cellular Cardiology 52(1):264 (2012)
Cardiac progenitor cells (CPCs) are multipotent cells that may offer tremendous potentials for the regeneration of injured myocardium. To expand the limited number of CPCs for effective clinical regeneration of myocardium, it is important to understand their proliferative potentials. Single-cell...
Phorbol ester and endothelin-1 alter functional expression of Na+/Ca2+ exchange, K+, and Ca2+ currents in cultured neonatal rat myocytes.
American Journal of Physiology - Heart and Circ... 300(2):H617 (2011)
Endothelin-1 (ET-1) and activation of protein kinase C (PKC) have been implicated in alterations of myocyte function in cardiac hypertrophy and heart failure. Changes in cellular Ca2+ handling and electrophysiological properties also occur in these states and may contribute to mechanical dysfunc...
Expression and roles of Cav1.3 (α1D) L-type Ca²+ channel in atrioventricular node automaticity.
Journal of Molecular and Cellular Cardiology 50(1):194 (2011)
Atrioventricular node (AV node) is the hub where electrical input from the atria is propagated and conveyed to the ventricles. Despite its strategic position and role in governing impulse conduction between atria and ventricles, there is paucity of data regarding the contribution of specific ion...
Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of Galphaq protein-induced cardiomyopathy.
American Journal of Physiology - Heart and Circ... 299(5):H1459 (2010)
Adenylyl cyclase (AC) is the principal effector molecule in the β-adrenergic receptor pathway. AC(V) and AC(VI) are the two predominant isoforms in mammalian cardiac myocytes. The disparate roles among AC isoforms in cardiac hypertrophy and progression to heart failure have been under intense in...
Cardiac small conductance Ca2+-activated K+ channel subunits form heteromultimers via the coiled-coil domains in the C termini of the channels.
Circulation Research 107(7):851 (2010)
Ca(2+)-activated K(+) channels are present in a wide variety of cells. We have previously reported the presence of small conductance Ca(2+)-activated K(+) (SK or K(Ca)) channels in human and mouse cardiac myocytes that contribute functionally toward the shape and duration of cardiac action poten...
Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches.
Journal of Molecular and Cellular Cardiology 47(6):835 (2009)
Myocardial infarction (MI) leading to myocardial cell loss represents one of the common causes leading to cardiac failure. We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase (sEH) inhibitors in cardiac hypertrophy. sEH catalizes the conversion of e...
Alpha-actinin2 cytoskeletal protein is required for the functional membrane localization of a Ca2+-activated K+ channel (SK2 channel).
PNAS 106(43):18402 (2009)
The importance of proper ion channel trafficking is underpinned by a number of channel-linked genetic diseases whose defect is associated with failure to reach the cell surface. Conceptually, it is reasonable to suggest that the function of ion channels depends critically on the precise subcellu...
Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation.
Journal of Physiology 587(Pt 5):1087 (2009)
Small conductance Ca(2+)-activated K(+) channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(2+)(i)) with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac m...
Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches
Journal of Molecular and Cellular Cardiology 47(6):835 (2009)
Myocardial infarction (MI) leading to myocardial cell loss represents one of the common causes leading to cardiac failure. We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase (sEH) inhibitors in cardiac hypertrophy. sEH catalizes the conversion...
Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes.
Circulation Research 102(4):465 (2008)
Since the first description of the anatomical atrioventricular nodes (AVNs), a large number of studies have provided insights into the heterogeneity of the structure as well as a repertoire of ion channel proteins that govern this complex conduction pathway between the atria and ventricles. Thes...
Ablation of sarcolipin enhances sarcoplasmic reticulum calcium transport and atrial contractility.
PNAS 104(45):17867 (2007)
Sarcolipin is a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) and is expressed abundantly in atria. In this study we investigated the physiological significance of sarcolipin in the heart by generating a mouse model deficient for sarcolipin. The sarcolipin-null mice ...
Molecular coupling of a Ca2+-activated K+ channel to L-type Ca2+ channels via alpha-actinin2.
Circulation Research 100(1):112 (2007)
Cytoskeletal proteins are known to sculpt the structural architecture of cells. However, their role as bridges linking the functional crosstalk of different ion channels is unknown. Here, we demonstrate that a small conductance Ca(2+)-activated K(+) channels (SK2 channel), present in a variety o...
Prevention and reversal of cardiac hypertrophy by soluble epoxide hydrolase inhibitors.
PNAS 103(49):18733 (2006)
Sustained cardiac hypertrophy represents one of the most common causes leading to cardiac failure. There is emerging evidence to implicate the involvement of NF-kappaB in the development of cardiac hypertrophy. However, several critical questions remain unanswered. We tested the use of soluble e...