Transient outward K+ current (ITO) reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp study in human and rabbit cardiac atrial myocytes

A.J. Workman, G.E. Marshall, A.C. Rankin, G.L. Smith, J. Dempster

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background & aim. Human atrial transient outward K+ current (ITO) is decreased in a variety of cardiac pathologies, but how ITO reduction alters action potentials (AP) and arrhythmia mechanisms is poorly understood, owing to non-selectivity of ITO blockers. Aim: to investigate effects of selective ITO changes on AP shape and duration (APD), and on afterdepolarisations or abnormal automaticity with beta-adrenergic-stimulation, using the dynamic-clamp technique in atrial cells. Methods & Results. Human and rabbit atrial cells were isolated by enzymatic dissociation, and electrical activity recorded by whole-cell-patch clamp (35-37oC). Dynamic-clamp-simulated ITO reduction or block slowed AP phase 1 and elevated the plateau, significantly prolonging APD, in both species. In human atrial cells, ITO block (100% ITO subtraction) increased APD50 by 31%, APD90 by 17%, and APD-61mV (reflecting cellular effective refractory period) by 22% (P
Original languageEnglish
Pages (from-to)4289–4305
Number of pages17
JournalJournal of Physiology
Volume590
Issue number17
Early online date25 Jun 2012
DOIs
Publication statusPublished - Sep 2012

Keywords

  • K+ current
  • cardiac atrial myocytes
  • ion current
  • dynamic clamp
  • atrial cells

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