Properties and ionic mechanisms of a metabotropic glutamate receptor-mediated slow afterdepolarization in neocortical neurons.
1. Pyramidal neurons from layer V of rat neocortex were recorded intracellularly in a brain slice preparation to study their response to stimulation of metabotropic glutamate receptors (mGluRs) by bath application of the selective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the nonselective agonists glutamate and quisqualate. 2. The principal postsynaptic effect of mGluR stimulation in the presence of ionotropic glutaminergic and muscarinic cholinergic antagonists was the appearance of a slow afterdepolarization (ADP) after evoked spikes. Only an afterhyperpolarization (AHP) was present in control perfusate. After 20 spikes evoked individually at 100 Hz the ADP peaked at 317 +/- 117 (SD) ms after the spike train, ranged from 1 to 12 mV in peak amplitude, and decayed over 7.4 +/- 4.7 s. This effect was not blocked by L-2-amino-3-phosphono-propionic acid (1 mM). Spikes evoked in the presence of the ionotropic glutamate receptor agonist R,S-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) did not have an ADP. 3. A detectable ADP appeared at concentrations of 0.1 microM quisqualate or 0.5 microM 1S,3R-ACPD. Maximum ADP amplitude was obtained with 5 microM quisqualate or 100 microM 1S,3R-ACPD. The ADP appeared after a single evoked spike in most cells tested and ADP amplitude increased to a maximum as the number of spikes evoked at 100 Hz was increased to between 5 and 20. 4. The ionic mechanisms underlying the ADP were examined by ion substitution and the application of channel-blocking agents. No difference in ADP amplitude was observed when the recording electrode contained CH3SO4. instead of Cl.. The ADP was present after 3 mM extracellular Cs+ were added to block the hyperpolarization-activated cation current or when 100 microM Ba2+ were included to block voltage-gated K+ currents. The ADP was abolished when Mn2+ was substituted for Ca2+ in the perfusate or when the Ca2+ chelator 5,5'-dimethyl-bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid was included in the recording electrode. A large ADP followed Ca2+ spikes evoked in the presence of 1 microM tetrodotoxin with 20 mM tetraethylammonium in the perfusate or with Cs+ substituted for K+ in the recording electrode. The amplitude of the ADP after the Ca2+ spikes was reduced by 49% when extracellular Na+ concentration was reduced from 136 to 26 mM. 5. The voltage dependence of the ADP was examined in relation to K+ equilibrium potential (EK).(ABSTRACT TRUNCATED AT 400 WORDS)
Greene
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Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle 98195.
Schwindt
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Crill
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D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002540:Cerebral Cortex / Q000502:physiology*; D046508:Culture Techniques; D004558:Electric Stimulation; D005260:Female; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; D000244:Adenosine Diphosphate