Transient outward potassium current and Ca2+ homeostasis in the heart: beyond the action potential

Bassani, Rosana A.

doi:10.1590/s0100-879x2006000300010

Cited by 29 publications

(21 citation statements)

References 55 publications

(106 reference statements)

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“…As the main current to be modified in post-MI LV dysfunction, I to current density constitutes an excellent electrophysiological marker of LV remodeling (2,44). Moreover, despite a large regional variability, a homogeneous reduction of I to density in all ventricular compartments (LV free wall and apex, septum, and right ventricle) has been reported in MI rats (1).…”

Section: Discussionmentioning

confidence: 99%

Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling

Ceconi

Comini

Suffredini

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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The aim of this study was to investigate the effect of chronic heart rate (HR) reduction with the hyperpolarization-activated current inhibitor ivabradine on the global phenotype of left ventricular (LV) remodeling in a ligated rat model. Seven days after coronary artery ligation, Wistar rats received ivabradine (10 mg · kg(-1) · day(-1) administered in drinking water) [myocardial infarction + ivabradine (MI+IVA), n = 22] or vehicle only (drinking water) (MI, n = 20) for 90 days. A sham group (n = 20) was included for model validation. MI+IVA rats had 12% lower HR (P < 0.01), improved LV volumes, 15% higher LV ejection fraction (LVEF, P < 0.01) than MI rats, and 33% reductions in both plasma atrial natriuretic peptide (ANP, P = 0.052) and cardiac hydroxyproline. Using patch-clamp, action potential duration was reduced and transient outward current density increased (P < 0.05). Cardiac energy metabolism was also improved (+33% creatine phosphate, P < 0.001; +15% ATP; and +9% energy charge, P < 0.05). Significant correlations were found between HR and parameters of cardiac metabolism, ANP, and LVEF (all P < 0.05). The HR-reducing properties of ivabradine prevent changes in the global phenotype of LV remodeling in the rat, optimize energy consumption, and avoid electrophysiological and structural remodeling.

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Section: Discussionmentioning

confidence: 99%

Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling

Ceconi

Comini

Suffredini

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Our findings demonstrate that AP prolongation alone can markedly enhance E-C coupling in normal myocytes through increases in the L-type Ca 2+ current (I Ca,L ) trigger combined with modest enhancements in Ca 2+ release efficiency [32]. In rat, dog, rabbit, and human myocytes, I to is prominent and plays a significant role in the early repolarization phase of the AP [33][34][35][36][37]. During an excitation, Ca 2+ enters into the cytosol with repeated rapid pacing and more Ca 2+ influx is expected.…”

Section: Discussionmentioning

confidence: 73%

Ionic Mechanisms Underlying Action Potential Prolongation by Focal Cerebral Ischemia in Rat Ventricular Myocytes

Wang

Sun

Hui-wei

et al. 2009

Cell Physiol Biochem

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Despite prolongation of the QTc interval in humans during cerebral ischemia, little is known about the mechanisms that underlie these actions. Cerebral ischemic model was established by middle cerebral artery occlusion (MCAO) for 24 h. In rat ventricular myocytes, the effect of cerebral ischemia on action potential duration (APD) and underlying electrophysiologic mechanisms were investigated by whole-cell patch clamp. We demonstrated that heart rate-corrected QT interval and APD were prolonged with frequent occurrence of ventricular tachyarrhythmias in a rat model of MCAO. The I_Na density was overall smaller in cerebral ischemic myocytes relative to sham myocytes (P < 0.01). The Nav1.5 protein and mRNA levels (pore-forming subunit for I_Na ) were decreased by about 20% (P < 0.01) in cerebral ischemic rat hearts than those in sham-operated rat hearts. Peak transient outward K⁺ current (I_to) at +60 mV was found decreased by ∼ 32.3% (P < 0.01) in cerebral ischemic rats. The peak amplitude of L-type Ca²⁺ current (I_Ca,L) was increased and the inactivation kinetics were slowed (P < 0.01). Protein level of the pore-forming subunit for I_to was decreased, but that for I_Ca,L was increased. The inward rectifier K⁺ current (I_K1) at -120 mV and its protein level were unaffected. Our study represents the first documentation of I_Na, I_to and I_Ca,L channelopathy as the major ionic mechanism for cerebral ischemic QT prolongation.

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“…Note that action potential duration is lengthened markedly and also that the initial repolarization phase or notch of the action potential disappears. Given the role of I K1 , I KS , and I Kr in late repolarization (during phase 3) of the ventricular action potential [33,35,36], the reduction in APD 90 and depolarization of myocyte RMP with progressive K + channel block were entirely predictable consequences.…”

Section: Simulations Of Heart Failure In Ventricular Myocytesmentioning

confidence: 99%

Mathematical Simulations of Sphingosine-1-Phosphate Actions on Mammalian Ventricular Myofibroblasts and Myocytes

MacCannell

Chilton

Smith

et al. 2015

Cardiac Fibrosis and Heart Failure: Cause or Effect?

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Mathematical modeling has been used to explore the consequences of the actions of sphingosine-1-phosphate (S-1-P) within the ventricular myocardium. Electrophysiological data obtained from rabbit cultured myofibroblasts [1] provided the basis for formulation of our model of electrotonic coupling between ventricular myocytes and fibroblasts [2]. Specifically, our in silico fibroblast/myocyte hybrid model was modified to account for the electrophysiological properties that are characteristic of the myofibroblast (the wound healing phenotype of the fibroblast). In addition, equations describing an S-1-P-induced current that can be activated in the myofibroblast were added.The sets of simulations that constitute this paper demonstrate that S-1-P can cause a significant depolarization of the resting membrane potential in both the myofibroblast and myocyte. When the myocyte to fibroblast coupling ratio is 1:1, this concentration-dependent effect is due to ligand-gated current in the myofibroblast depolarizing the myocyte through heterotypic connexin-mediated intercellular junctions. In addition to changing the resting potential in the myocyte, the S-1-P induced current resulted in significant changes in action potential waveform.A second set of simulations was done for the purpose of exploring the effects of S-1-P on myocytes that have some of the main electrophysiological properties of those from the failing heart. In these computations, the ten is associated with heart failure), resulted in prolongation of action potential duration. Simulations of electrotonic coupling between this model 'failing' myocyte and myofibroblasts demonstrated that the resting potential and APD in the failing myocyte is more susceptible to modulation by electrotonic influences from S-1-Pstimulated myofibroblasts when a 'failing' electrophysiological phenotype in the ventricular myocyte is introduced. In summary, our simulations draw attention to important effects of S-1-P on the ventricular myocardium even when this paracrine substance acts only on the fibroblast cell population. These cell-specific S-1-P effects alter the myocyte action potential via electrotonic coupling. It is apparent that myofibroblasts can have significant effects on myocyte action potentials; and that these effects would be expected to be more pronounced in the presence of ligand-gated effects on the myofibroblast. The general setting that we have attempted to replicate with this first order model has some similarities to acute or sterile inflammation in the myocardium wherein S-1-P concentrations in the interstitium are relatively high.

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Transient outward potassium current and Ca2+ homeostasis in the heart: beyond the action potential

Abstract: The present review deals with Ca 2+

Cited by 29 publications

References 55 publications

Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling

Heart rate reduction with ivabradine prevents the global phenotype of left ventricular remodeling

Ionic Mechanisms Underlying Action Potential Prolongation by Focal Cerebral Ischemia in Rat Ventricular Myocytes

Mathematical Simulations of Sphingosine-1-Phosphate Actions on Mammalian Ventricular Myofibroblasts and Myocytes

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