Referenced in: none

Automatically associated channels: Kv11.1

Title: Inhibition of HERG K+ current and prolongation of the guinea-pig ventricular action potential by 4-aminopyridine.

Authors: J M Ridley, J T Milnes, Y H Zhang, H J Witchel, J C Hancox

Journal, date & volume: J. Physiol. (Lond.), 2003 Jun 15 , 549, 667-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12740430

Abstract
4-Aminopyridine (4-AP) has been used extensively to study transient outward K+ current (ITO,1) in cardiac cells and tissues. We report here inhibition by 4-AP of HERG (the human ether-à-go-go-related gene) K+ channels expressed in a mammalian cell line, at concentrations relevant to those used to study ITO,1. Under voltage clamp, whole cell HERG current (IHERG) tails following commands to +30 mV were blocked with an IC50 of 4.4 +/- 0.5 mM. Development of block was contingent upon HERG channel gating, with a preference for activated over inactivated channels. Treatment with 5 mM 4-AP inhibited peak IHERG during an applied action potential clamp waveform by ~59 %. It also significantly prolonged action potentials and inhibited resurgent IK tails from guinea-pig isolated ventricular myocytes, which lack an ITO,1. We conclude that by blocking the alpha-subunit of the IKr channel, millimolar concentrations of 4-AP can modulate ventricular repolarisation independently of any action on ITO,1.