Activation of δ-opioid receptors inhibits L-type Ca(2+) current and transient outward K(+) current in rat ventricular myocytes.
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.
Lin
Yuan-Yuan
YY
Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
Wu
Dong-Mei
DM
Liu
Lei
L
Liu
Qing-Hua
QH
Yan
Zhe-Yi
ZY
Wu
Bo-Wei
BW
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001549:Benzamides / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists*
C484285:((+)-4-((alphaR)-alpha-((2S,5R)-2,5-dimethyl-4-(2-propenyl)-1-piperazinyl)-(3-phenyl)methyl)-N,N-diethylbenzamide); D000889:Anti-Arrhythmia Agents; D001549:Benzamides; D020746:Calcium Channels, L-Type; D010879:Piperazines; D015221:Potassium Channels; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole