Metabotropic glutamate receptor agonist-induced hyperpolarizations in rat basolateral amygdala neurons: receptor characterization and ion channels

Abstract

1. Metabotropic glutamate receptor (mGluR)-agonist-induced hyperpolarizations and corresponding outward currents were analyzed in basolateral amygdala (BLA) neurons in rat brain slice preparations with current-clamp and single-electrode voltage-clamp recording to characterize the mGluR subtype(s) and the ion channel(s) mediating this response. 2. The mGluR agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induced a membrane hyperpolarization or outward current in BLA neurons in a concentration-dependent manner (median effective concentration = 34 microM; range = 10-200 microM); the 1S,3R-ACPD hyperpolarizations are recorded in 89% of neurons that accommodate or cease firing in response to a 400-ms depolarizing current injection (0.5 nA). 3. mGluR agonists elicited hyperpolarizations or outward currents in a concentration-dependent manner in the following rank order of potency: (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) > 1S,3R-ACPD > (s)-4-carboxyphenylglycine = (RS)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) > L-aminophosphonobutyric acid > (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid. In contrast, the mGluR agonists quisqualate and ibotenate induced only depolarizations in the presence of D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione in BLA neurons. 4. The 1S,3R-ACPD-induced outward current is mediated through a large-conductance calcium-dependent potassium (BK) conductance. The BK channel blockers iberiotoxin and charybdotoxin blocked the response, as did the potassium channel blockers tetraethylammonium and 4-aminopyridine; the small-conductance calcium-activated potassium channel blocker apamin did not affect the response. 5. The mGluR-agonist-induced hyperpolarization is blocked in amygdala slices from animals pretreated with pertussis toxin (PTX). 1S,3R-ACPD hyperpolarizations were recorded in neurons contralateral but not ipsilateral to the site of PTX injection. 6. The antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) reduced significantly the 1S,3R-ACPD-induced hyperpolarization. 7. In conclusion, the relative potency of L-CCG-I and 4C3HPG in evoking only hyperpolarizations (outward currents) in accommodating neurons, and the observation that MCPG (500 microM) reduces the hyperpolarization, suggest that a group-II-like mGluR underlies the hyperpolarizing response. The mGluR-induced response is sensitive to iberiotoxin and to pretreatment with PTX, suggesting activation of BK channels through a group II mGluR linked to a PTX-sensitive G protein in BLA neurons.

Quisqualate‐preferring metabotropic glutamate receptor activates Na(+)‐Ca2+ exchange in rat basolateral amygdala neurones.

“…The multiple responses to IS,3R-ACPD agree with previous reports from this laboratory (Rainnie et al 1994;Holmes et al 1996a, b) IS,3R-ACPD (50 FM) produced an inward current with a mean peak amplitude of 26 + 13 pA (n = 9) in the absence, and 31 + 14 pA (n = 8) in the presence of D-APV, CNQX and TTX; similarly, 1S,3R-ACPD (100 #M) induced currents of 43 + 9 (n = 16) and 35 + 12 pA (n = 13) in the absence and presence of D-APV, CNQX and TTX, respectively. All subsequent experiments were conducted in the constant presence of these antagonists.…”

“…This laboratory has previously reported that, in neurones of the basolateral amygdala, the mGlu agonists trans-and 1S,3R-ACPD predominantly evoke an outward current that is typically followed by inward current (Rainnie et al 1994). It was further shown that the outward current is mediated through a group II-like mGlu coupled to large conductance (BK) calcium-dependent potassium channels (Holmes, Keele, Arvanov & Shinnick-Gallagher, 1996a). The mechanism underlying the inward current is unknown, but it is increased in amplitude following amygdala kindling-induced epileptogenesis (Holmes, Keele & Shinnick-Gallagher, 1996b).…”

Selective Activation of mGlu4 Metabotropic Glutamate Receptors Is Protective against Excitotoxic Neuronal Death

“…Similar to other group III mGluRs (Saugstad et al, 1996(Saugstad et al, , 1997Corti et al, 1998), mGluR4 receptors positively couple to inwardly rectifying K ϩ channels in amphibian oocytes (Sharon et al, 1997). L-AP-4 can also activate K ϩ channels in CNS neurons (Holmes et al, 1996;Dutar et al, 1999). Through this mechanism, activation of mGluR4 might affect neuronal sensitivity to excitotoxic damage independently of changes in glutamate release.…”

Glutamate Receptors on the Somata of Dorsal Unpaired Median Neurons in Cockroach, Periplaneta americana, Thoracic Ganglia

“…Application of 1S, 3R-ACPD at concentrations of 1 mM resulted in membrane hyperpolarization in DUM neurons. Hyperpolarizing responses produced by activation of postsynaptic mGluRs with 1S, 3R-ACPD also have been shown in neurons of the rat basolateral amygdala (Rainnie et al ., 1994;Holmes et al ., 1996). They suggested from their studies that the hyperpolarization is G-proteine mediated and results from activation of a TEA-sensitive, calcium-dependent potassium conductance.…”