Metabotropic glutamate receptor agonist ACPD inhibits some, but not all, muscarinic-sensitive K+ conductances in basolateral amygdaloid neurons.
Muscarinic agonists produce membrane depolarization and losses of spike frequency accommodation and the slow afterhyperpolarization (AHP) when applied to neurons of the basolateral amygdala (BLA). Underlying these changes are the muscarinic-induced inhibitions of several K+ conductances, including the voltage-activated M-current (IM), a slowly decaying Ca(2+)-activated current (IAHP), a voltage-insensitive leak current (ILeak), and the hyperpolarization-activated inward rectifier current (IIR). Similar depolarizations and losses of the slow AHP have been observed in other neuronal cell types following stimulation of metabotropic glutamate receptors. Therefore, we tested the effects of the metabotropic glutamate receptor agonist, 1-aminocyclopentane-1s,3R-dicarboxylic acid (ACPD), on pyramidal neurons impaled with a single microelectrode for current- and voltage-clamp recordings in a brain slice preparation of the rat BLA. Application of ACPD (20 or 100 microM) to BLA neurons inhibited IM and IAHP, resulting in membrane depolarization and reductions in the amplitude and duration of the slow AHP. However, ACPD did not inhibit the muscarinic-sensitive current IIR, nor was ILeak blocked in the majority of neurons examined. These findings suggest the possibility that muscarinic cholinergic and metabotropic glutamatergic receptor agonists may activate separate intracellular transduction pathways which have convergent inhibitory effects onto IM and IAHP in BLA pyramidal neurons.
Womble
M D
MD
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Moises
H C
HC
D000200:Action Potentials / Q000187:drug effects; D000669:Amplifiers, Electronic; D000679:Amygdala / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009498:Neurotoxins / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D009498:Neurotoxins; D010277:Parasympathomimetics; D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D013779:Tetrodotoxin; D002118:Calcium