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Journal of Neuroscience, Vol 15, 4315-4327, Copyright © 1995 by Society for Neuroscience
mu-Opioid receptor activation reduces multiple components of high- threshold calcium current in rat sensory neurons
KI Rusin and HC Moises
Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Whole-cell patch-clamp recordings were used to characterize calcium channel
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 sensitivity to the
selective channel blockers omega-conotoxin GVIA, nifedipine,
omega-conotoxin MVIIC, or omega-agatoxin IVA. The mu-opioid selective
agonist Tyr-Pro-NMePhe-D-Pro-NH2 (PLO17) routinely suppressed
high-threshold currents and this effect was always reduced by omega-
conotoxin GVIA. A fraction of PLO17-sensitive current remained after
omega-conotoxin GVIA that was eliminated by application of omega- agatoxin
IVA alone or in combination with omega-conotoxin MVIIC. Nifedipine had no
effect on mu-opioid responses nor did PLO17 affect the slow component of
tail current induced by Bay K 8644. These data suggest that mu-opioid
receptors are negatively coupled to three types of calcium channels in rat
DRG neurons, including an omega-conotoxin GVIA-sensitive (N-type) channel,
an omega-agatoxin IVA-sensitive (P- type) channel and an omega-conotoxin
MVIIC-sensitive, nifedipine/GVIA/omega-Aga IVA-resistant (presumptive
Q-type) channel.
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