Effects of Agonists of μ-Opioid Receptors on P-Type Calcium Channels in Rat Purkinje Neurons

Calcium channels of the P-type play an important role in synaptic transmission in the CNS of mammals; the major part of calcium ions entering the presynaptic terminal comes precisely via these channels. Using the whole-cell patch-clamp technique, we studied the effects of mu-opioids on P-type calcium channels in freshly isolated Purkinje neurons of the rat cerebellum. A selective agonist of mu-opioid receptors, DAMGO (10 nM), caused stable moderate (10 +/- 1%, on average) but significant (D < 0.001; n = 27) potentiation of P-type current in most units. This effect of DAMGO was rather appreciable already at a concentration of 1 nM and reached saturation at 100 nM. The effect developed rapidly (in about 10 sec); it was voltage-dependent and completely reversible. An endogenous selective agonist of mu-opioid receptors, endorphin-1, evoked nearly the same effect (increment 8 +/- 1%, n = 6, P < 0.01). DAMGO-caused increase in the amplitude of P-type currents was completely removed after application of an antagonist of opioid receptors, naloxone (100 nM). These data indicate that agonists of mu-opioid receptors, even in nanomolar concentrations, can evoke appreciable potentiation of P-type calcium current mediated by interaction with opioid receptors of the corresponding type.