Properties of GABA-mediated synaptic potentials induced by zinc in adult rat hippocampal pyramidal neurones.
1. Intracellular recording techniques were used to study the actions of the transition ion, zinc, on CA1 and CA3 pyramidal neurones in adult rat hippocampal slices. 2. Zinc (300 microM) hyperpolarized pyramidal neurones, increased the membrane excitability and also induced periodic, spontaneous giant depolarizing potentials associated with a conductance increase mechanism. 3. The occurrence of spontaneous giant depolarizations was dependent on the zinc concentration (10 microM-1 mM) with an apparent dissociation constant of 98 microM. The frequency of zinc-induced depolarizations was unaffected by the membrane potential from -50 to -100 mV. 4. Stimulation of the Schaffer collaterals or mossy fibre pathways evoked an excitatory and inhibitory synaptic potential complex. In the presence of zinc, nerve fibre stimulation evoked, in an all-or-none fashion, a giant depolarizing potential with an increased membrane conductance. Both spontaneous and evoked depolarizations were inhibited by 1 microM tetrodotoxin. 5. Evoked giant depolarizations were labile with too frequent stimulation resulting in a failure of generation. A minimum time of 140 s was required between stimuli to ensure successive giant depolarizations. 6. Spontaneous and evoked zinc-induced depolarizing potentials were inhibited by bicuculline (10 microM) or picrotoxin (40 microM) and enhanced by pentobarbitone (100 microM) or flurazepam (10 microM), suggesting that these potentials are mediated by activation of gamma-aminobutyric acidA (GABAA) receptors. 7. Ionophoretic application of GABA produced biphasic responses at -60 mV membrane potential. The reversal potentials for the depolarizing and hyperpolarizing GABA responses were -56 +/- 5 and -66 +/- 8 mV respectively. The giant depolarizations induced by zinc reversed at -57 +/- 4 mV. This suggests a dendritic location for the generation of these potentials. 8. Excitatory amino acid antagonists, 2-amino-5-phosphonovalerate (APV, 40 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) did not affect the amplitude but slightly reduced the frequency of the giant depolarizations. 9. It is concluded that zinc induces a synchronized release of GABA, quite independent of intact excitatory synaptic transmission, which acts on GABAA receptors producing large depolarizing synaptic potentials. This increased level of GABA release may be of physiological and pathological importance since zinc is a naturally occurring metal ion endogenous to the central nervous system.
School of Pharmacy, Department of Pharmacology, London.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D046508:Culture Techniques; D005479:Flurazepam / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001640:Bicuculline; D005479:Flurazepam; D010424:Pentobarbital; D010852:Picrotoxin; D015032:Zinc; D005680:gamma-Aminobutyric Acid