Current density as routine parameter for description of ionic membrane current: is it always the best option?

Prog Biophys Mol Biol. 2020 Nov:157:24-32. doi: 10.1016/j.pbiomolbio.2019.11.011. Epub 2019 Nov 30.

Abstract

The current density (J) is a parameter routinely used to characterize individual ionic membrane currents. Its evaluation is based on the presumption that the magnitude of whole-cell ionic membrane current (I) is directly proportional to the cell membrane capacitance (C), i.e. I positively and strongly correlates with C and the regression line describing I-C relation intersects the y-axis close to the origin of coordinates. We aimed to prove the presumption in several examples and find whether the conversion of I to J could be always beneficial. I-C relation was analysed in several potassium currents, measured in rat atrial myocytes (in inward rectifier currents, IK1, and both the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current, IK(Ach)CONST and IK(Ach)ACH), and in rat ventricular myocytes (transient outward current Ito). I-C correlation was estimated by the Pearson coefficient (r). A coefficient (k) was newly suggested describing deviation of the regression intercept from zero in currents with considerable r value. Based on mathematical simulations, I was satisfactorily proportional to C when r ≥ 0.6 and k ≤ 0.2 which was fulfilled in IK1 and IK(Ach)ACH (r = 0.84, k = 0.20, and r = 0.61, k = 0.06, respectively). I-C correlation was significantly positive, but weak in IK(Ach)CONST (r = 0.42), and virtually missing in Ito (r = 0.04). The impaired I-C proportionality in IK(Ach)CONST and Ito likely reflects heterogeneity of the channel expression. We conclude that the conversion of I to J should be avoided when I-C proportionality is absent. Otherwise, serious misinterpretation of data may arise.

Keywords: Current density; Current-capacitance correlation; Current-capacitance proportionality; Ionic current; Normalisation by ratio; Rat cardiomyocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / chemistry
  • Animals
  • Cell Membrane / physiology*
  • Electric Capacitance
  • Electrophysiology
  • Genotype
  • Heart Atria / pathology
  • Ions
  • Male
  • Membrane Potentials / drug effects
  • Models, Theoretical
  • Muscle Cells / cytology*
  • Myocardium
  • Myocytes, Cardiac / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Ions
  • Acetylcholine