Stimulation of opioid receptors on cardiac ventricular myocytes reduces L type Ca2+ channel current.
Recent studies have indicated that opioid peptide receptors are present on cardiac ventricular cells and that Leucine enkephalin (LE), a naturally occurring delta opioid peptide receptor agonist, leads to marked reductions in twitch amplitude and in the cytosolic Ca2+ transient (Ca(i)) of single adult rat ventricular myocytes. The specific mechanisms by which Ca(i) is reduced by LE have not been fully elucidated. Specifically, it is unknown whether LE affects the Ca2+ current (ICa) of L type Ca2+ channels. In the present study we determined the effect of LE on ICa of individual cardiac ventricular cells freshly isolated from adult rats. LE (10(-8) M) decreased the amplitude of ICa by 40% (during regular whole cell voltage clamp depolarizations to 0 mV at 0.5 Hz at 23 degrees C from a holding potential of -40 mV). The relative magnitude of this effect increased with the magnitude of the test potential from -20 to +50 mV. ICa inactivation was also prolonged by LE. These effects of LE on ICa were abolished by Naloxone (NAL), an opioid receptor antagonist. Thus, the effects of the opioid peptide, LE, to decrease the Ca(i) transient and contraction amplitudes in individual cardiac ventricular cells, are, in part, mediated by an LE induced reduction in ICa.
Xiao
R P
RP
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Spurgeon
H A
HA
Capogrossi
M C
MC
Lakatta
E G
EG
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004743:Enkephalin, Leucine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000032:analysis / Q000502:physiology*
D015220:Calcium Channels; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D004743:Enkephalin, Leucine