K. Endo et H. Yawo, mu-Opioid receptor inhibits N-type Ca2+ channels in the calyx presynaptic terminal of the embryonic chick ciliary ganglion, J PHYSL LON, 524(3), 2000, pp. 769-781
1. A study was made on the mechanisms by which enkephalins inhibit synaptic
transmission at calyx-type presynaptic terminals in the ciliary ganglion o
f chick embryos at stages 39-40.
2. Excitatory postsynaptic currents (EPSCs) were recorded by nystatin-perfo
rated patch clamp at low [Ca2+](o) and high [Mg2+](o). [Leu(5)]enkephalin (
L-ENK, 1-10 mu M) reduced the quantal content (m) without changing the quan
tal size (q). This effect was antagonized by naloxone (1 mu M). Similar res
ults were observed under conventional whole-cell clamp of the postsynaptic
neuron.
3. A specific agonist of the mu-opioid receptor, [D-Ala(2), M-Me-Phe(4),Gly
(5)]enkephalin-ol (DAMGO) reduced m without changing q. A specific agonist
of the delta-opioid receptor, [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) also r
educed m without changing q.
4. Both L-ENK and [Met(5)]enkephalin (M-ENK) reduced the stimulus-dependent
increment of the intraterminal Ca2+ concentration (Delta[Ca2+](t)) without
affecting the decay time constant of the intraterminal Ca2+ concentration
and basal Ca2+ level. This effect was antagonized by naloxone. DAMGO reduce
d Delta[Ca2+](t) more effectively than DPDPE.
5. When extracellular Ca2+ was replaced by Ba2+, the stimulus-dependent inc
rement of the intraterminal Ba2+ concentration (Delta[Ba2+](t)) was also re
duced by L-ENK or DAMGO.
6. L-ENK reduced Delta[Ca2+](t) even in the presence of 4-aminopyridine (4-
AP), which blocks the transient K+ conductance during the falling phase of
the presynaptic action potential. When N-type Ca2+ channels were blocked by
omega-conotoxin GVIA (omega-CgTx(GVIA)), the Delta[Ca2+)(t) was no longer
sensitive to L-ENK and DAMGO.
7. It is suggested that enkephalins reduce the transmitter release through
presynaptic opioid receptors. The mu-opioid receptor may suppress presynapt
ic Ca2+ influx by selectively inhibiting N-type Ca2+ channels.