Elevated potassium outward currents in hyperoxia treated atrial cardiomyocytes

J Cell Physiol. 2018 May;233(5):4317-4326. doi: 10.1002/jcp.26263. Epub 2017 Dec 26.

Abstract

Supplementation of 100% oxygen is a very common intervention in intensive care units (ICU) and critical care centers for patients with dysfunctional lung and lung disorders. Although there is advantage in delivering sufficient levels of oxygen, hyperoxia is reported to be directly associated with increasing in-hospital deaths. Our previous studies reported ventricular and electrical remodeling in hyperoxia treated mouse hearts, and in this article, for the first time, we are investigating the effects of hyperoxia on atrial electrophysiology using whole-cell patch-clamp electrophysiology experiments along with assessment of Kv1.5, Kv4.2, and KChIP2 transcripts and protein profiles using real-time quantitative RT-PCR and Western blotting. Our data showed that induction of hyperoxia for 3 days in mice showed larger outward potassium currents with shorter action potential durations (APD). This increase in current densities is due to significant increase in ultrarapid delayed rectifier outward K+ currents (IKur ) and rapidly activating, rapidly inactivating transient outward K+ current (Ito ) densities. We also observed a significant increase in both transcripts and protein levels of Kv1.5 and KChIP2 in hyperoxia treated atrial cardiomyocytes, whereas no significant change was observed in Kv4.2 transcripts or protein. The data presented here further support our previous findings that hyperoxia induces not only ventricular remodeling, but also atrial electrical remodeling.

Keywords: atria; cardiomyocytes; hyperoxia; rapidly inactivating transient outward K+ current (Ito) arrhythmias; ultrarapid delayed rectifier outward K+ current (IKur) rapidly activating; whole-cell electrophysiology.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Gene Expression Regulation
  • Heart Atria / physiopathology
  • Hospital Mortality
  • Humans
  • Hyperoxia / etiology
  • Hyperoxia / physiopathology
  • Intensive Care Units
  • Kv Channel-Interacting Proteins / genetics*
  • Kv1.6 Potassium Channel / genetics*
  • Lung / metabolism
  • Lung / physiopathology
  • Lung Diseases / complications
  • Lung Diseases / mortality
  • Lung Diseases / physiopathology
  • Lung Diseases / therapy*
  • Mice
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology
  • Oxygen / adverse effects*
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Shal Potassium Channels / genetics*

Substances

  • Kv Channel-Interacting Proteins
  • Kv1.6 Potassium Channel
  • Shal Potassium Channels
  • Potassium
  • Oxygen