MU-OPIOID RECEPTOR ACTIVATION REDUCES MULTIPLE COMPONENTS OF HIGH-THRESHOLD CALCIUM CURRENT IN RAT SENSORY NEURONS

Whole-cell patch-clamp recordings were used to characterize calcium ch annel types that are modulated by mu-opioid receptor activation in rat dorsal root ganglion (DRG) neurons. Five distinct components of high- threshold calcium current were isolated on the basis of their sensitiv ity to the selective channel blockers omega-conotoxin GVIA, nifedipine , omega-conotoxin MVIIC, or omega-agatoxin IVA. The mu-opioid selectiv e agonist Tyr-Pro-NMePhe-D-Pro-NH2 (PL017) routinely suppressed high-t hreshold currents and this effect was always reduced by omega-conotoxi n GVIA. A fraction of PL017-sensitive current remained after omega-con otoxin GVIA that was eliminated by application of omega-agatoxin IVA a lone or in combination with omega-conotoxin MVIIC. Nifedipine had no e ffect on mu-opioid responses nor did PL017 affect the slow component o f tail current induced by Bay K 8644, These data suggest that mu-opioi d receptors are negatively coupled to three types of calcium channels in rat DRG neurons, including an omega-conotoxin GVIA-sensitive (N-typ e) channel, an omega-agatoxin IVA-sensitive (P-type) channel and an om ega-conotoxin MVIIC-sensitive, nifedipine/GVIA/omega-Aga IVA-resistant (presumptive Q-type) channel.