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Stimulation of opioid receptors on cardiac ventricular myocytes reduces L type Ca2+ channel current
R P Xiao1, H A Spurgeon, M C Capogrossi
1Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
Abstract:
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.
Insights
Leucine enkephalin (LE) reduces cardiac cell contractions by decreasing calcium currents (ICa) through L-type calcium channels. This effect is mediated by delta opioid receptors and blocked by naloxone.
Area of Science:
- Cardiovascular Physiology
- Neuropharmacology
- Molecular Cardiology
Background:
- Opioid peptide receptors are found on cardiac ventricular cells.
- Leucine enkephalin (LE), a delta opioid agonist, reduces myocyte contractility and calcium transients.
- The precise mechanism of LE-induced calcium reduction is not fully understood.
Purpose of the Study:
- To investigate the effect of Leucine enkephalin (LE) on the calcium current (ICa) in adult rat ventricular myocytes.
- To determine if LE modulates L-type calcium channels in the heart.
Main Methods:
- Whole-cell voltage clamp recordings were performed on freshly isolated adult rat ventricular myocytes.
- The effect of LE (10(-8) M) on L-type calcium current (ICa) was measured.
- Naloxone (NAL), an opioid receptor antagonist, was used to assess the involvement of opioid receptors.
Main Results:
- LE significantly decreased the amplitude of ICa by 40%.
- The inhibitory effect of LE on ICa was voltage-dependent, increasing with depolarization.
- LE prolonged the inactivation of ICa.
- Naloxone abolished the effects of LE on ICa, confirming opioid receptor mediation.
Conclusions:
- Leucine enkephalin reduces cardiac contractility, in part, by inhibiting the L-type calcium current in ventricular myocytes.
- This action is mediated through delta opioid receptors on cardiac cells.
- The findings elucidate a key cellular mechanism underlying the cardiac effects of opioid peptides.