Effects of U50,488H on transient outward and ultra-rapid delayed rectifier K+ currents in young human atrial myocytes.
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.
Xiao
Guo-Sheng
GS
Department of Physiology, Faculty of Medicine, The University of Hong Kong, Laboratory Block, 21 Sassoon Road, Hong Kong SAR, China.
Zhou
Jing-Jun
JJ
Cheung
Yiu-Fai
YF
Li
Gui-Rong
GR
Wong
Tak-Ming
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D006325:Heart Atria; D006801:Humans; D007223:Infant; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024683:Potassium Channels, Tandem Pore Domain; D024642:Potassium Channels, Voltage-Gated; D017473:Receptors, Opioid, kappa / Q000819:agonists
D051668:Delayed Rectifier Potassium Channels; D009292:Narcotic Antagonists; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D024642:Potassium Channels, Voltage-Gated; D017473:Receptors, Opioid, kappa; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer