Activation of δ-opioid receptors inhibits L-type Ca(2+) current and transient outward K(+) current in rat ventricular myocytes

Sheng Li Xue Bao. 2008 Feb 25;60(1):38-42.

Abstract

In the present study, whole-cell patch-clamp technique was used to observe the effects of SNC162, a selective agonist of δ-opioid receptors, on L-type Ca(2+) current (I(Ca-L)) and transient outward K(+) current (I(to)) in rat ventricular myocytes. The results showed that SNC162 significantly inhibited I(Ca-L) and I(to) in rat ventricular myocytes. The maximal inhibition rate of I(Ca-L) and I(to) reached (46.13±4.12)% and (36.53±10.57)%, respectively. SNC162 at 1×10(-4) mol/L inhibited the current density of I(Ca-L) from (8.98±0.40) pA/pF to (4.84±0.44) pA/pF (P<0.01, n=5) and inhibited that of I(to) from (18.69±2.42) pA/pF to (11.73±1.67) pA/pF (P<0.01, n=5). Furthermore, the effects of naltrindole, a highly selective antagonist of δ-opioid receptors, on I(Ca-L) and I(to) were also observed. The results showed that naltrindole alone had no effects on I(Ca-L) and I(to), while it abolished the inhibitory effects of SNC162 on I(Ca-L) and I(to). In conclusion, SNC162 concentration-dependently inhibited I(Ca-L) and I(to) in rat ventricular myocytes via activation of the δ-opioid receptors, which may be a fundamental mechanism underlying the antiarrhythmic effect of activating δ-opioid receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents
  • Benzamides / pharmacology*
  • Calcium Channels, L-Type / metabolism*
  • Cells, Cultured
  • Heart Ventricles / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Patch-Clamp Techniques
  • Piperazines / pharmacology*
  • Potassium Channels / metabolism*
  • Rats
  • Receptors, Opioid, delta / agonists*

Substances

  • ((+)-4-((alphaR)-alpha-((2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl)-(3-phenyl)methyl)-N,N-diethylbenzamide)
  • Anti-Arrhythmia Agents
  • Benzamides
  • Calcium Channels, L-Type
  • Piperazines
  • Potassium Channels
  • Receptors, Opioid, delta
  • Naltrexone
  • naltrindole