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 δ 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 mechanism by which Ca_i is reduced by LE have not been fully elucidated. Specifically, it is unknown whether LE affects the Ca²⁺ current (I_Ca) of L type Ca²⁺ channels. In the present study we determined the effect of LE on I_Ca of individual cardiac ventricular cells freshly isolated from adult rats. LE (10^-8M) decreased the amplitude of I_Ca by 40% (during regular whole cell voltage clamp depolarizations to 0 mV at 0.5 Hz at 23°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. I_Ca inactivation was also prolonged by LE. These effects of LE on I_Ca 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 I_Ca .