Jeffrey R. Balser

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Our objective was to develop a DNA biobank linked to phenotypic data derived from an electronic medical record (EMR) system. An "opt-out" model was implemented after significant review and revision. The plan included (i) development and maintenance of a de-identified mirror image of the EMR, namely, the "synthetic derivative" (SD) and (ii) DNA extracted(More)
A dynamic positive feedback mechanism, known as ‘facilitation’, augments L-type calcium-ion currents (ICa) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CaM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are(More)
1. Upon depolarization, voltage-gated sodium channels assume non-conducting inactivated states which may be characterized as "fast' or "slow' depending on the length of the repolarization period needed for recovery. Skeletal muscle Na+ channel alpha-subunits expressed in Xenopus laevis oocytes display anomalous gating behaviour, with substantial slow(More)
Prolongation of cardiac action potentials may mediate some of the arrhythmia-suppressing and arrhythmia-aggravating actions of antiarrhythmic agents. In this study, suppression of time-dependent outward current by quinidine and amiodarone was assessed in guinea pig ventricular myocytes. The net time-dependent outward current contained at least two(More)
The normal electrophysiologic behavior of the heart is determined by ordered propagation of excitatory stimuli that result in rapid depolarization and slow repolarization, thereby generating action potentials in individual myocytes. Abnormalities of impulse generation, propagation, or the duration and configuration of individual cardiac action potentials(More)
Disulfide trapping studies have revealed that the pore-lining (P) segments of voltage-dependent sodium channels undergo sizable motions on a subsecond time scale. Such motions of the pore may be necessary for selective ion translocation. Although traditionally viewed as separable properties, gating and permeation are now known to interact extensively in(More)
The coincident cloning of the voltage-gated Na channel from the electric eel electroplax and development of patch-clamp methodology has allowed an explosive phase of investigation into the structural basis of cardiac Na channel function. Recognizing the importance of structural motifs that underlie gating (charged S4 segments, III-IV linker) and permeation(More)
BACKGROUND Mutations in the gene encoding the human cardiac sodium channel (SCN5A) have been associated with three distinct cardiac arrhythmia disorders: the long QT syndrome, the Brugada syndrome and cardiac conduction disease. Here we report the biophysical features of a novel sodium channel mutation, E161K, which we identified in individuals of two(More)
Cardiac sodium (Na) channels are dynamic molecules that undergo rapid structural changes in response to the changing electrical field in the myocardium. Inherited mutations in SCN5A, the gene encoding the cardiac Na channel, provoke life-threatening cardiac arrhythmias, often by modifying these voltage-dependent conformational changes. These disorders (i.e.(More)
Large-scale DNA databanks linked to electronic medical record (EMR) systems have been proposed as an approach for rapidly generating large, diverse cohorts for discovery and replication of genotype-phenotype associations. However, the extent to which such resources are capable of delivering on this promise is unknown. We studied whether an EMR-linked DNA(More)