The Journal of Neurophysiology Vol. 78 No. 6 December 1997, pp. 3428-3437
Copyright ©1997 The American Physiological Society

Modulation of Multiple Potassium Currents by Metabotropic Glutamate Receptors in Neurons of the Hypothalamic Supraoptic Nucleus

L. A. Schrader and J. G. Tasker

Neuroscience Training Program and Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118

Schrader, L. A. and J. G. Tasker. Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons of the hypothalamic supraoptic nucleus. J. Neurophysiol. 78: 3428-3437, 1997. 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 µm) of the rat hypothalamus. Trans-(±)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 10-100 µM), a broad-spectrum metabotropic glutamate receptor agonist, evoked an inward current (18.7 ± 3.45 pA) or a slow depolarization (7.35 ± 4.73 mV) and a 10-30% decrease in whole cell conductance in ~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 because 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 (I_A) by 20-70% and/or the I_A-mediated delay to spike generation in ~60% of magnocellular neurons tested. The cells that showed a reduction of I_A 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 (I_AHP) in ~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, a group I receptor-selective agonist, mimicked the effects of trans-ACPD on the resting and voltage-gated K⁺ currents. (RS)--methyl-4-carboxyphenylglycine, a group I/II metabotropic glutamate receptor antagonist, blocked these effects. A group II receptor agonist, 2S,1S,2S-2carboxycyclopropylglycine and a group III receptor agonist, L(+)-2-amino-4-phosphonobutyric acid, 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 labeled immunohistochemically for vasopressin responded to metabotropic glutamate receptor activation, whereas 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.

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