Intrinsic proton modulation of excitatory transmission in rat hippocampal slices.
Recent work suggests that activity-induced alkaline transients within the interstitial space of nervous tissue are largely due to net fluxes of acid-base equivalents across postsynaptic receptor-gated ion channels. In view of the marked pH sensitivity of certain receptor channels, it has been frequently postulated that synaptically-evoked H+ shifts might play a neuromodulatory role. We provide here the first evidence to support the above hypothesis in showing that extracellularly recorded glutamatergic responses in area CA1 of rat hippocampal slices are potentiated upon inhibition of fast extracellular H+ buffering by a poorly-permeant carbonic anhydrase inhibitor, benzolamide (10 microM). Experiments with glutamate receptor antagonists and Mg(2+)-free solutions suggest that the action of benzolamide is mediated by the H+ sensitivity of N-methyl-D-aspartate (NMDA) receptor channels. In further agreement with an intrinsic neuromodulatory role for H+ in excitatory transmission, addition of the H+ buffer HEPES (20 mM) produced a selective attenuation of pharmacologically-isolated NMDA receptor-mediated responses.
Taira
T
T
Department of Zoology, University of Helsinki, Finland.
Smirnov
S
S
Voipio
J
J
Kaila
K
K
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001574:Benzolamide / Q000494:pharmacology; D002021:Buffers; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005971:Glutamates / Q000502:physiology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D011522:Protons; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002021:Buffers; D005971:Glutamates; D011522:Protons; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001574:Benzolamide