• Publications
  • Influence
Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na+ channel blockade and to increases in heart rate. Implications for gene-specific therapy.
TLDR
This is the first study to demonstrate differential responses of LQTS patients to interventions targeted to their specific genetic defect, and it is suggested that LQT3 patients may be more likely to benefit from Na+ channel blockers and from cardiac pacing because they would be at higher risk of arrhythmia at slow heart rates.
The Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative - Update on progress.
Improving the In Silico Assessment of Proarrhythmia Risk by Combining hERG (Human Ether-à-go-go-Related Gene) Channel–Drug Binding Kinetics and Multichannel Pharmacology
TLDR
Modeling dynamic drug–hERG channel interactions and multi-ion channel pharmacology improves the prediction of torsadogenic risk and has the potential to improve the regulatory assessment of drug safety models under the CiPA paradigm.
Biomarkers of Endothelial Cell Activation Serve as Potential Surrogate Markers for Drug-induced Vascular Injury
TLDR
This review alerts pharmaceutical companies, research institutions, and regulatory agencies to the continuing need for reliable biomarkers of EC activation in drug development.
Block of delayed rectifier potassium current, IK, by flecainide and E-4031 in cat ventricular myocytes.
TLDR
IK block by E-4031 most likely underlies the drug's potent class III antiarrhythmic properties, but this effect may be obscured by concomitant block of plateau Na+ channels to produce little or no change in action potential duration, consistent with its class IC classification.
Optimization of an In silico Cardiac Cell Model for Proarrhythmia Risk Assessment
TLDR
A new model with scaled conductances calculated by fitting to O'Hara et al. in vitro human cardiomyocyte channel blocking experiments is presented, which improves discrepancies of the original model and improves the effect of INaL block on action potential prolongation, an important determinant of proarrhythmia risk in the context of CiPA.
Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibres.
  • T. Colatsky
  • Biology
    The Journal of physiology
  • 1 August 1980
TLDR
It is concluded that the approach described is valid for measurements of sodium currents in the potential range where action potentials are initiated, making it possible to study cardiac sodium channels in an adult mammalian preparation which is free of enzymatic treatment.
Modulation of the delayed rectifier, IK, by cadmium in cat ventricular myocytes.
TLDR
The effects of cadmium on the delayed outward potassium current (IK) were investigated in isolated cat ventricular myocytes using the single suction pipette voltage-clamp technique and Cd2+ did not alter channel selectivity for K+.
A New Perspective in the Field of Cardiac Safety Testing through the Comprehensive In Vitro Proarrhythmia Assay Paradigm
TLDR
The rationale, progress, and challenges for the CiPA initiative are reviewed, if this new paradigm is to replace existing practice and, in time, lead to improved and widely accepted cardiac safety testing guidelines.
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