TY - JOUR
T1 - Transient outward K+ current (ITO) reduction prolongs action potentials and promotes afterdepolarisations
T2 - a dynamic-clamp study in human and rabbit cardiac atrial myocytes
AU - Workman, A.J.
AU - Marshall, G.E.
AU - Rankin, A.C.
AU - Smith, G.L.
AU - Dempster, J.
PY - 2012/9
Y1 - 2012/9
N2 - 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
AB - 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
KW - K+ current
KW - cardiac atrial myocytes
KW - ion current
KW - dynamic clamp
KW - atrial cells
UR - http://www.scopus.com/inward/record.url?scp=84865581574&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2012.235986
DO - 10.1113/jphysiol.2012.235986
M3 - Article
C2 - 22733660
VL - 590
SP - 4289
EP - 4305
JO - Journal of Physiology
JF - Journal of Physiology
IS - 17
ER -