PT - JOURNAL ARTICLE AU - Rui-Lin Wu AU - Michael E. Barish TI - Modulation of a Slowly Inactivating Potassium Current,<em>I</em><sub>D</sub>, by Metabotropic Glutamate Receptor Activation in Cultured Hippocampal Pyramidal Neurons AID - 10.1523/JNEUROSCI.19-16-06825.1999 DP - 1999 Aug 15 TA - The Journal of Neuroscience PG - 6825--6837 VI - 19 IP - 16 4099 - http://www.jneurosci.org/content/19/16/6825.short 4100 - http://www.jneurosci.org/content/19/16/6825.full SO - J. Neurosci.1999 Aug 15; 19 AB - ID is a slowly inactivating 4-aminopyridine (4-AP)-sensitive potassium current of hippocampal pyramidal neurons and other CNS neurons. AlthoughID exerts multifaceted influence on CNS excitability, whether ID is subject to modulation by neurotransmitters or neurohormones has not been clear.We report here that one prominent effect of metabotropic glutamate receptor (mGluR) activation by short (3 min) exposure to 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (100 μm) is suppression of ID by acceleration of its inactivation. ID was identified as a target of mGluR-mediated modulation because inactivation of a component of outward current sensitive to 100–200 μm4-AP was accelerated by 1S,3R-ACPD, and because 4-AP occluded any further actions of 1S,3R-ACPD. Enhancement ofID inactivation was induced by the group I-preferring agonist RS-3,5-dihydroxyphenylglycine (3,5-DHPG) and the group II-preferring agonist 2S,2′R,3′R)-2-(2′,3′dicarboxycyclopropyl)-glycine (DCG-IV), but not by the group III-preferring agonistl(+)-2-amino-4-phosphonobutyric acid (L-AP4); it was blocked by the broadly acting mGluR antagonistS-α-methyl-4-carboxyphenylglycine (S-MCPG). Furthermore, inactivation of ID was enhanced by inclusion of GTPγS in the internal solution and blocked by inclusion of GDPβS.Metabotropic GluR-induced suppression of IDwas manifest in three aspects of excitability previously linked toID by their sensitivity to 4-AP: reduction in input conductance and enhanced excitability at voltages just positive to the resting potential, reduced delay to action potential firing during depolarizing current injections, and delayed action potential repolarization. We suggest that mGluR-induced suppression ofID could contribute to enhancement of hippocampal neuron excitability and synaptic connections.