Injury current modulates afterdepolarizations in single human ventricular cells.
OBJECTIVE
Injury current (I(injury)) and afterdepolarizations are thought to play an important role in arrhythmias that occur during acute ischemia. However, little is known about the effects of I(injury) on afterdepolarizations. The present study was designed to study the effect of I(injury) on afterdepolarizations and action potentials in single human ventricular cells.


METHODS
The patch-clamp technique was used to record action potentials and to apply I(injury) to human ventricular cells. In these cells, early and delayed afterdepolarizations (EADs and DADs) were induced by 1 microM norepinephrine. I(injury) was simulated by coupling cells via a variable coupling resistance to a passive resistance circuit with a potential of 0, -20, or -40 mV, mimicking a depolarized ischemic region.


RESULTS
At all potentials, I(injury) induced depolarization of the resting membrane potential and action potential shortening. Flowing from 0 mV, I(injury) induced EADs by itself and aggravated the EADs and DADs that were induced by norepinephrine. Flowing from -40 mV, I(injury) abolished the noradrenaline-induced EADs and DADs.


CONCLUSIONS
Our results demonstrate that I(injury) may either prevent or promote the occurrence of afterdepolarizations in human ventricle. The latter holds if conduction is slowed to such an extent that it permits flow of current from depolarized ischemic cells at plateau level to cells in phase 3 or phase 4.
Verkerk
A O
AO
Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. A.O.Verkerk@amc.uva.nl
Veldkamp
M W
MW
de Jonge
N
N
Wilders
R
R
van Ginneken
A C
AC
D000200:Action Potentials / Q000187:drug effects*; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000503:physiopathology; D006352:Heart Ventricles; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques
D009638:Norepinephrine