Modulation of Multiple Potassium Currents by Metabotropic Glutamate
Receptors inNeurons of the Hypothalamic Supraoptic Nucleus.
L.A. Schrader and J.G. Tasker.
Neuroscience Training Program and Dept. of Cell and Molecular Biology
Tulane University, New Orleans, LA 70118.
APStracts 4:177N, 1997.
ABSTRACT
We studied the effects of activation of the metabotropic glutamate receptors
on intrinsic currents of magnocellular neurons of the supraoptic nucleus (SON)
with whole-cell patch-clamp and conventional intracellular recordings in
coronal slices (400 æm) of the rat hypothalamus. Trans-(ñ)-1-amino-1,3-
cyclopentane dicarboxylic acid (trans-ACPD, 10-100 æM), a broad spectrum
metabotropic glutamate receptor agonist, evoked an inward current (18.7 ñ 3.45
pA) or a slow depolarization (7.35 ñ 4.73 mV) and a 10-30% decrease in whole-
cell conductance in approximately 50% of the magnocellular neurons recorded at
resting membrane potential. The decrease in conductance and the inward current
were caused largely by the attenuation of a resting potassium conductance,
since they were reduced by the replacement of intracellular potassium with an
equimolar concentration of cesium, or by the addition of potassium channel
blockers to the extracellular medium. In some cells, trans-ACPD still elicited
a small inward current after blockade of potassium currents, which was
abolished by the calcium channel blocker, CdCl2. Trans-ACPD also reduced
voltage-gated and Ca2+-activated K+ currents in these cells. Trans-ACPD
reduced the transient outward current (IA) by 20-70%, and/or the IA-mediated
delay to spike generation in about 60% of magnocellular neurons tested. The
cells that showed a reduction of IA generally also showed a 20-60% reduction
in a voltage-gated, sustained outward current. Finally, trans-ACPD attenuated
the Ca2+-dependent outward current responsible for the afterhyperpolarization
(IAHP) in about 60% of cells tested. This often revealed an underlying inward
current thought to be responsible for the depolarizing afterpotential seen in
some magnocellular neurons. (RS)-3,5-dihydroxyphenylglycine (DHPG), a group I
receptor-selective agonist, mimicked the effects of trans-ACPD on the resting
and voltage-gated K+ currents. (RS)-à-methyl-4-carboxyphenylglycine (MCPG), a
group I/II metabotropic glutamate receptor antagonist, blocked these effects.
A group II receptor agonist, 2S,1'S,2'S-2 carboxycyclopropylglycine (L-CCG-I)
and a group III receptor agonist, L(+)-2-amino-4-phosphonobutyric acid (L-
AP4), had no effect on the resting or voltage-gated K+ currents, indicating
that the reduction of K+ currents was mediated by group I receptors. About 80%
of the SON cells that were immunohistochemically labeled for vasopressin
responded to metabotropic glutamate receptor activation, while only 33% of
labeled oxytocin cells responded, suggesting that metabotropic receptors are
expressed preferentially in vasopressinergic neurons. These data indicate that
activation of the group I metabotropic glutamate receptors leads to an
increase in the postsynaptic excitability of magnocellular neurons by blocking
resting K+ currents, as well as by reducing voltage-gated and Ca2+-activated
K+ currents.
Received 2 December 1996; accepted in final form 30 July 1997.
APS Manuscript Number J938-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997