Kv1.5 is an important component of repolarizing K+ current in canine atrial myocytes

Circ Res. 2003 Oct 17;93(8):744-51. doi: 10.1161/01.RES.0000096362.60730.AE. Epub 2003 Sep 18.

Abstract

Although the canine atrium has proven useful in several experimental models of atrial fibrillation and for studying the effects of rapid atrial pacing on atrial electrical remodeling, it may not fully represent the human condition because of reported differences in functional ionic currents and ion channel subunit expression. In this study, we reassessed the molecular components underlying one current, the ultrarapid delayed rectifier current in canine atrium [IKur(d)], by evaluating the mRNA, protein, immunofluorescence, and currents of the candidate channels. Using reverse transcriptase-polymerase chain reaction, we found that Kv1.5 mRNA was expressed in canine atrium whereas message for Kv3.1 was not detected. Western analysis on cytosolic and membrane fractions of canine tissues, using selective antibodies, showed that Kv3.1 was only detectable in the brain preparations, whereas Kv1.5 was expressed at high levels in both atrial and ventricular membrane fractions. Confocal imaging performed on isolated canine atrial myocytes clearly demonstrated the presence of Kv1.5 immunostaining, whereas that of Kv3.1 was equivocal. Voltage- and current-clamp studies showed that 0.5 mmol/L tetraethylammonium had variable effects on sustained K+ currents, whereas a compound with demonstrated selectivity for hKv1.5 versus Kv3.1, hERG or the sodium channel, fully suppressed canine atrial IKur tail currents and depressed sustained outward K+ current. This agent also increased action potential plateau potentials and action potential duration at 20% and 50% repolarization. These results suggest that in canine atria, as in other species including human, Kv1.5 protein is highly expressed and contributes to IKur.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Atrial Function*
  • Cell Line
  • Cell Membrane / metabolism
  • Dogs
  • Electric Conductivity
  • Heart Atria / chemistry
  • Heart Atria / cytology
  • Humans
  • Kv1.5 Potassium Channel
  • Myocytes, Cardiac / chemistry
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Neuropeptides / analysis
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / analysis
  • Potassium Channels / physiology*
  • Potassium Channels, Voltage-Gated*
  • Shaw Potassium Channels

Substances

  • KCNA5 protein, human
  • Kv1.5 Potassium Channel
  • Neuropeptides
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Shaw Potassium Channels