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

Eur J Pharmacol. 2003 Jul 25;473(2-3):97-103. doi: 10.1016/s0014-2999(03)01974-5.

Abstract

The effects of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate salt (U50,488H), a selective kappa-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 microM), while at +50 mV, U50,488H produced biphasic effects on Ito1-increasing and decreasing the current at 1-3 and 10-30 microM, respectively. U50,488H at 10 microM shifted the midpoint (V0.5) of Ito1 activation in a depolarizing direction by approximately 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 microM). The effects of U50,488H on the two types of K+ currents were not antagonized by either 5 microM 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / pharmacology*
  • Adolescent
  • Child
  • Child, Preschool
  • Delayed Rectifier Potassium Channels
  • Female
  • Heart Atria
  • Humans
  • Infant
  • Male
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / physiology
  • Naloxone / pharmacology
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Patch-Clamp Techniques
  • Potassium Channels / drug effects*
  • Potassium Channels / physiology
  • Potassium Channels, Tandem Pore Domain*
  • Potassium Channels, Voltage-Gated*
  • Receptors, Opioid, kappa / agonists

Substances

  • Delayed Rectifier Potassium Channels
  • Narcotic Antagonists
  • Potassium Channels
  • Potassium Channels, Tandem Pore Domain
  • Potassium Channels, Voltage-Gated
  • Receptors, Opioid, kappa
  • Naloxone
  • norbinaltorphimine
  • Naltrexone
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer