Developmental changes in expression and biophysics of ion channels in the canine ventricle

J Mol Cell Cardiol. 2013 Nov;64:79-89. doi: 10.1016/j.yjmcc.2013.09.001. Epub 2013 Sep 10.

Abstract

Background: Developmental changes in the electrical characteristics of the ventricular myocardium are not well defined. This study examines the contribution of inwardly rectifying K(+) current (IK1), transient outward K(+) current (Ito), delayed rectifier K(+) currents (IKr and IKs) and sodium channel current (INa) to repolarization in the canine neonate myocardium.

Methods: Single myocytes isolated from the left ventricle of 2-3week old canine neonate hearts were studied using patch-clamp techniques.

Results: Neonate cells were ~6-fold smaller than those of adults (28.8±8.8 vs. 176±6.7pF). IK1 was larger in neonate myocytes and displayed a substantial inward component and an outward component with negative slope conductance, peaking at -60mV (4.13 pA/pF). IKr tail currents (at -40mV), were small (<20pA). IKs could not be detected, even after exposure to isoproterenol (100nM). Ito was also absent in the neonate, consistent with the absence of a phase 1 in the action potential. Peak INa, late INa and ICa were smaller in the neonate compared with adults. KCND3, KCNIP2 and KCNQ1 mRNA expression was half, while KCNH2 was equal and KCNJ2 was greater in the neonate when compared with adults.

Conclusions: Two major repolarizing K(+) currents (IKs and Ito) present in adult ventricular cells are absent in the 2week old neonate. Peak and late INa are significantly smaller in the neonate. Our results suggest that the absence of these two currents in the neonate heart may increase the susceptibility to arrhythmias under certain long QT conditions.

Keywords: Developmental electrophysiology; K(+) current; Sudden death; Ventricular arrhythmias.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Animals, Newborn
  • Anti-Arrhythmia Agents / pharmacology
  • Calcium / metabolism
  • Dogs
  • Female
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Humans
  • Ion Channels / genetics*
  • Ion Channels / metabolism*
  • Male
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology
  • Patch-Clamp Techniques
  • Piperidines / pharmacology
  • Potassium / metabolism
  • Potassium Channels / physiology
  • Pyridines / pharmacology
  • Sodium / metabolism
  • Ventricular Function / drug effects
  • Ventricular Function / physiology*

Substances

  • Anti-Arrhythmia Agents
  • Ion Channels
  • Piperidines
  • Potassium Channels
  • Pyridines
  • E 4031
  • Sodium
  • Potassium
  • Calcium