Ionic mechanisms of GABA-induced long-term potentiation in the rat superior colliculus.
GABA-induced excitation and long-term potentiation (LTPG) have been demonstrated recently in the superficial layers of the superior colliculus (SC). In other regions of the nervous system, GABA elicits excitatory responses via ionotropic GABA receptors under certain conditions. This excitation is proposed to be due to either a high neuronal chloride concentration favouring a depolarising chloride efflux, or to a bicarbonate efflux coupled to a chloride influx. The aim of this study was to characterise the mechanisms underlying excitation and prolonged increase in synaptic transmission induced by GABA in the SC. Extracellular field potentials were recorded from 1-month-old rat SC slices, and LTPG of these responses was evoked by application of 3 mM GABA. GABA-induced excitation and LTPG were significantly reduced by lowering the extracellular calcium concentration, but not by a decreased potassium concentration. Replacing the extracellular bicarbonate-buffered perfusion medium with a HEPES-buffered solution had no effect on LTPG but blocking the bicarbonate-generating enzyme carbonic anhydrase both intra- and extracellularly with ethoxyzolamide (50 microM) prevented LTPG. The chloride transport inhibitor bumetanide (50 microM) reduced but did not block LTPG. We therefore suggest that the contribution of the chloride equilibrium to LTPG is only of minor importance. The intracellular bicarbonate pool and related efflux provides the basis for the excitatory action of GABA, leading to a subsequent depolarisation and calcium influx through voltage-dependent calcium channels, thus causing long-lasting changes in synaptic transmission.
White
A M
AM
Department of Biomedical Sciences, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, AB25 2ZD, UK.
Platt
B
B
D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001639:Bicarbonates / Q000037:antagonists & inhibitors / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology; D005016:Ethoxzolamide / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011191:Potassium Deficiency / Q000503:physiopathology; D051381:Rats; D013477:Superior Colliculi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism*; D000096922:K Cl- Cotransporters
D001639:Bicarbonates; D002034:Bumetanide; D002118:Calcium; D002257:Carbonic Anhydrase Inhibitors; D002712:Chlorides; D004232:Diuretics; D005016:Ethoxzolamide; D005665:Furosemide; D007473:Ion Channels; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters