Isolation and morphology of calcium-tolerant feline ventricular myocytes

Silver, Lester; Hemwall, E L; Marino, Thomas A.; Houser, S. R.

doi:10.1152/ajpheart.1983.245.5.h891

Cited by 53 publications

(36 citation statements)

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“…Rodshaped myocytes were isolated from the left ventricles of normal rabbits via enzymatic digestion of the whole heart on a Langendorff apparatus, using common cell isolation techniques (23). Animals were euthanized by pentobarbital overdose (80 mg/kg intravenously).…”

Section: Methodsmentioning

confidence: 99%

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Nuss¹,

Marbán²,

Johns³

1999

J. Clin. Invest.

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The high incidence of sudden death in heart failure may reflect abnormalities of repolarization and heightened susceptibility to arrhythmogenic early afterdepolarizations (EADs). We hypothesized that overexpression of the human K + channel HERG (human ether-a-go-go-related gene) could enhance repolarization and suppress EADs. Adult rabbit ventricular myocytes were maintained in primary culture, which suffices to prolong action potentials and predisposes to EADs. To achieve efficient gene transfer, we created AdHERG, a recombinant adenovirus containing the HERG gene driven by a Rous sarcoma virus (RSV) promoter. The virally expressed HERG current exhibited pharmacologic and kinetic properties like those of native I Kr . Transient outward currents in AdHERG-infected myocytes were similar in magnitude to those in control cells, while stimulated action potentials (0.2 Hz, 37°C) were abbreviated compared with controls. The occurrence of EADs during a train of action potentials was reduced by more than fourfold, and the relative refractory period was increased in AdHERG-infected myocytes compared with control cells. Gene transfer of delayed rectifier potassium channels represents a novel and effective strategy to suppress arrhythmias caused by unstable repolarization.

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Section: Methodsmentioning

confidence: 99%

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Nuss¹,

Marbán²,

Johns³

1999

J. Clin. Invest.

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“…16 .50 C. Junction potentials between the pipette and external solution were about -8 mV. This potential was offset before the initiation of each experiment, and the data are uncorrected for this offset.…”

Section: Methodsmentioning

confidence: 99%

Block of delayed rectifier potassium current, IK, by flecainide and E-4031 in cat ventricular myocytes.

1990

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(Circulation 1990;82:289-293) T he delayed rectifier outward potassium current, IK, is believed to play a major role in repolarizing the cardiac action potential.' Selective block of IK has been shown to underlie the uniform increase in action potential duration (APD) produced by the class III antiarrhythmic agents,2-5 whereas many class I antiarrhythmic agents, such as quinidine and cibenzoline, possess K' channel blocking properties that contribute to their antiarrhythmic drug action as well as to their subclassification as members of class IA.6-8Flecainide is an antiarrhythmic agent with pronounced Na+ channel blocking properties that result in a marked depression of cardiac conduction at therapeutic drug concentrations.910 Ca21 current is also inhibited by flecainide but at somewhat higher concentrations than those noted for Na+ channel block." Although both of these actions would tend to shorten APD, as is typically observed in canine Purkinje fibers12'13 and at high concentrations in ventricular muscle,9 flecainide has been reported to increase ventricular APD in vitro,9'2 and to prolong monophasic ventricular APD in humans. '4 In clinical

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“…As mentioned in MATERIALS AND METHODS, normal contractions at a physiological pacing frequency (10 Hz) could not be sustained in isolated myocytes; thus, we could only obtain [Ca 2ϩ ] i transients at lower pacing frequencies (up to 3 Hz). This could be due to a number of factors, including cell damage during isolation, loss of structural integrity, and compromised metabolic properties (48,50). It is therefore possible that other aspects of Ca 2ϩ -handling properties are also affected.…”

Section: Model Validation (Wt Murine)mentioning

confidence: 99%

A mathematical model of the murine ventricular myocyte: a data-driven biophysically based approach applied to mice overexpressing the canine NCX isoform

Niederer

Idigo

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Li L, Niederer SA, Idigo W, Zhang YH, Swietach P, Casadei B, Smith NP. A mathematical model of the murine ventricular myocyte: a data-driven biophysically based approach applied to mice overexpressing the canine NCX isoform. Am J Physiol Heart Circ Physiol 299: H1045-H1063, 2010. First published July 23, 2010; doi:10.1152/ajpheart.00219.2010.-Mathematical modeling of Ca 2ϩ dynamics in the heart has the potential to provide an integrated understanding of Ca 2ϩ -handling mechanisms. However, many previous published models used heterogeneous experimental data sources from a variety of animals and temperatures to characterize model parameters and motivate model equations. This methodology limits the direct comparison of these models with any particular experimental data set. To directly address this issue, in this study, we present a biophysically based model of Ca 2ϩ dynamics directly fitted to experimental data collected in left ventricular myocytes isolated from the C57BL/6 mouse, the most commonly used genetic background for genetically modified mice in studies of heart diseases. This Ca 2ϩ dynamics model was then integrated into an existing mouse cardiac electrophysiology model, which was reparameterized using experimental data recorded at consistent and physiological temperatures. The model was validated against the experimentally observed frequency response of Ca 2ϩ dynamics, action potential shape, dependence of action potential duration on cycle length, and electrical restitution. Using this framework, the implications of cardiac Na ϩ / Ca 2ϩ exchanger (NCX) overexpression in transgenic mice were investigated. These simulations showed that heterozygous overexpression of the canine cardiac NCX increases intracellular Ca 2ϩ concentration transient magnitude and sarcoplasmic reticulum Ca 2ϩ loading, in agreement with experimental observations, whereas acute overexpression of the murine cardiac NCX results in a significant loss of Ca 2ϩ from the cell and, hence, depressed sarcoplasmic reticulum Ca 2ϩ load and intracellular Ca 2ϩ concentration transient magnitude. From this analysis, we conclude that these differences are primarily due to the presence of allosteric regulation in the canine cardiac NCX, which has not been observed experimentally in the wild-type mouse heart. calcium transient; C57BL/6 mouse; Na ϩ /Ca 2ϩ exchanger THE RHYTHMIC CONTRACTION of the heart is dependent on tightly regulated intracellular events triggered in a concerted fashion by electrical stimulation. Among a number of regulatory steps, Ca 2ϩ plays, arguably, the most fundamental role in orchestrating the excitation-contraction coupling process. (34, 59). With the large amount of experimental data in the mouse now becoming available, mathematical modeling has the potential power to rationalize the data and provide an integrated understanding of the mouse heart. Previously, Bondarenko and colleagues (6) developed a biophysically based electrophysiology model of murine left ventricular (LV) myocytes. However, several limitations with t...

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Isolation and morphology of calcium-tolerant feline ventricular myocytes

Cited by 53 publications

References 0 publications

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Overexpression of a human potassium channel suppresses cardiac hyperexcitability in rabbit ventricular myocytes

Block of delayed rectifier potassium current, IK, by flecainide and E-4031 in cat ventricular myocytes.

A mathematical model of the murine ventricular myocyte: a data-driven biophysically based approach applied to mice overexpressing the canine NCX isoform

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