Functional coupling between human E‐type Ca2+ channels and μ opioid receptors expressed in Xenopus oocytes

Neuronal α1E Ca2+ channels were expressed in Xenopus laevis oocytes alone and in combination with the μ opioid receptor. Macroscopic currents were recorded under voltage clamp conditions. The stimulation of the morphine receptor by the synthetic [d‐Ala2,N‐Me‐Phe4,Gly‐ol5] enkephalin (DAMGO) produced a 20% reduction in the α1E ionic current. This effect was associated with a large change in the decay phase of the Ba2+ current. The effect of 1 μM DAMGO was fully antagonized by the universal μ opioid receptor antagonist naloxone and by the selective antagonist β‐funaltrexamine. The ionic current inhibition induced by DAMGO was partially recovered by preceding strong depolarizations. The injection of the catalytic subunit of pertussis toxin (A‐protomer) abolished the effect of DAMGO, suggesting the involvement of a GTP binding protein in the α1E modulation. The coexpression of the regulatory β2a Ca2+ channel subunit, together with the α1E subunit and the μ opioid receptor, prevented the reduction of the ionic current following the receptor stimulation with DAMGO, whereas the coexpression with the β3 subunit reduced by ∼50% the modulatory effect of DAMGO. The effect produced by the stimulation of the opioid receptor could be mimicked by coexpressing the α1E channel with the G‐protein βγ subunits.