Variability in reported midpoints of (in)activationof cardiac INa

Abstract

Electrically active cells like cardiomyocytes show variability in their size, shape, and electrical activity. But should we expect variability in the properties of their ionic currents? In this brief review we gather and visualise measurements of two important electrophysiological parameters: the midpoints of activation and inactivation of the cardiac fast sodium current, INa. We find a considerable variation in reported mean values between experiments, with a smaller cell-to-cell variation within experiments. We show how the between-experiment variability can be decomposed into a correlated and an uncorrelated component, and that the correlated component is much larger and affects both midpoints almost equally. We then review biological and methodological issues that might explain the observed variability, and attempt to classify each as within-experiment or correlated and uncorrelated between-experiment factors. Although the existence of some variability in measurements of ionic currents is well-known, we believe that this is the first work to systematically review it and that the scale of the observed variability is much larger than commonly appreciated, which has implications for modelling and experimental design.