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Journal of Neuroscience, Vol 14, 7608-7615, Copyright © 1994 by Society for Neuroscience
Opioid receptors modulate diverse types of calcium channels in the nucleus tractus solitarius of the rat
H Rhim and RJ Miller
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
We have investigated the coupling between opioid receptors and different
types of Ca2+ channels in neurons acutely isolated from the nucleus tractus
solitarius (NTS) of the rat. Using fura-2-based imaging we found that Ca2+
transients evoked by depolarization with 50 mM KCl were suppressed by the
mu-opioid receptor agonist D-Ala2,N-MePhe4,Gly5- ol-enkephalin (DAMGO) and
less effectively by the kappa-receptor agonist U-69,593. The delta-receptor
agonist D-Pen2,D-Pen5-enkephalin (DPDPE) was ineffective. In whole-cell
voltage-clamp recordings from these neurons, depolarizing voltage steps
elicited high-threshold Ca2+ currents that could be distinguished
pharmacologically into different components. Part of the current could be
blocked by dihydropyridines, part by omega-conotoxin-GVIA and part by
omega-agatoxin-IVA. This suggests that the neurons contained L-, N-, and
P/Q-type Ca2+ channels. DAMGO and U-69,593 both blocked part of the Ca2+
current but DPDPE was ineffective. Perfusion of GTP-gamma-S into the cells
produced a rapid rundown of the Ca2+ current and occluded further effects
of the opioid agonists, suggesting the involvement of a G-protein in the
coupling mechanism. Inhibition of L-channels did not alter the effect of
DAMGO. On the other hand inhibition of N-channels occluded about 80% of the
effect of DAMGO. Inhibition of the P/Q-current occluded the remainder of
the DAMGO effect. Thus, it appears that activation of opioid receptors can
inhibit N- and P/Q-type Ca2+ channels but not L-channels in these cells. It
is likely that such effects are important in opioid- mediated inhibition of
transmitter release in the brain.
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