Effects of U50,488H on transient outward and ultra-rapid delayed rectifier K+ currents in young human atrial myocytes

Abstract

The effects of trans-(±)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate salt (U50,488H), a selective κ-opioid receptor agonist, on transient outward K+ current (Ito1) and ultra-rapid delayed rectifier K+ current (IKur) in young human atrial myocytes were evaluated with a whole-cell patch-clamp technique. At +10 mV, U50,488H decreased Ito1 in a concentration-dependent manner (IC50=12.4±3.5 μM), while at +50 mV, U50,488H produced biphasic effects on Ito1 - increasing and decreasing the current at 1-3 and 10-30 μM, respectively. U50,488H at 10 μM shifted the midpoint (V0.5) of Ito1 activation in a depolarizing direction by ∼5 mV, accelerated the inactivation, and slowed the recovery from inactivation of Ito1. In addition, U50,488H inhibited IKur in a concentration-dependent manner (IC50=3.3±0.6 μM). The effects of U50,488H on the two types of K+ currents were not antagonized by either 5 μM nor-binaltorphimine or 300 nM naloxone. These results indicate that U50,488H affects both Ito1 and IKur in young human atrial myocytes in an opioid receptor-independent manner. © 2003 Elsevier B.V. All rights reserved.