Nicotinic acetylcholine receptor-mediated synaptic potentials in rat neocortex.
In the neocortex, fast excitatory synaptic transmission can typically be blocked by using excitatory amino acid (EAA) receptor antagonists. In recordings from layer II/III neocortical pyramidal neurons, we observed an evoked excitatory postsynaptic potential (EPSP) or current (EPSC) in the presence of EAA receptor antagonists (40-100 microM D-APV+20 microM CNQX, or 5 mM kynurenic acid) plus the GABA(A)-receptor antagonist bicuculline (BIC, 20 microM). This EAA-antagonist resistant EPSC was observed in about 70% of neurons tested. It had a duration of approximately 20 ms and an amplitude of 61.5+/-6.8 pA at -70 mV (n=35). The EAA-antagonist resistant EPSC current-voltage relation was linear and reversed near 0 mV (n=23). The nonselective nicotinic acetylcholine receptor (nAChR) antagonists dihydro-beta-erythroidine (DH beta E, 100 microM) or mecamylamine (50 microM) reduced EPSC amplitudes by 42 (n=20) and 33% (n=9), respectively. EPSC kinetics were not significantly changed by either antagonist. Bath application of 10 microM neostigmine, a potent acetylcholinesterase inhibitor, prolonged the EPSC decay time. EAA-antagonist resistant EPSCs were observed in the presence of antagonists of metabotropic glutamate, serotonergic (5-HT(3)) and purinergic (P2) receptors. The EAA-antagonist resistant EPSC appears to be due in part to activation of postsynaptic nAChRs. These results suggest the existence of functional synaptic nAChRs on pyramidal neurons in rat neocortex.
Chu
Z G
ZG
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Zhou
F M
FM
Hablitz
J J
JJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007736:Kynurenic Acid / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D009388:Neostigmine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D004079:Dihydro-beta-Erythroidine; D009388:Neostigmine; D008464:Mecamylamine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D000110:Acetylcholinesterase; D007736:Kynurenic Acid; D001640:Bicuculline