Dynamic Clamp

Mutations in KCNH2 (hERG) underlie the long-QT2 syndrome. Most long-QT2 mutations produce a trafficking defect resulting in a decrease in n, the number of functional channels on the cell surface. Some mutations can also alter gating characteristics. The short-QT syndrome generally relates to shifts in the voltage dependence of inactivation to more depolarized potentials results in less inward rectification at physiological potentials and a larger time-dependent current at the expense of the magnitude of the repolarizing tail current.Article see p 1265Altomare et al1 provide conceptual advances in understanding the relative contributions of changes in gating features and gmax to action potential duration (APD) and its temporal variance. They should be congratulated for their innovative experimental approach and the interesting results. The insights that they provide seem to have clinical relevance.Altomare et al1 substituted the innate guinea pig rectifier K+ current ( I Kr) with injection of a modeled and programmable I Kr. This approach allows an assessment of the impact of programmable changes in the characteristics of I Kr on temporal variance on APD in the context of an otherwise native guinea pig cardiac action potential. This also allows requisite changes in cycle length elicited by a command potential in action potential clamp mode.They examined temporal variability in repolarization.1 Poincare plots allowed an assessment of the dynamics of the beat-to-beat variability of APD. Two metrics of beat-to-beat variability were computed: …