Differential effects of zinc on hyperpolarizing and depolarizing GABAA synaptic potentials in hippocampal slice cultures.
We have examined the changes in GABAA-mediated synaptic potentials recorded from CA3 pyramidal neurons in hippocampal slice cultures following application of zinc (Zn2+). Unlike 4-AP, Zn2+ did not enhance fast hyperpolarizing potentials but primarily enhanced depolarizing GABAA potentials. Zn2+ did not alter the postsynaptic response of pyramidal neurons to pressure applied GABA, consistent with previous reports that Zn2+ enhances the release of GABA from presynaptic terminals. To examine the role of local circuitry in the production of Zn2+ responses, we recorded from cultures maintained for 7-10 days following removal of the dentate and hilus to allow complete degeneration of the mossy fibers (DGX cultures). Zn2+ produced giant depolarizing potentials (GDPs) in DGX cultures that were identical to those in intact cultures. In contrast, the 4-AP response was dramatically altered in DGX cultures. In DGX cultures, Zn2+ co-applied with 4-AP appeared to inhibit the production of fast hyperpolarizing GABAA synaptic potentials produced by 4-AP alone. This inhibition of fast hyperpolarizing potentials suggests that Zn2+ may reduce the release of GABA onto pyramidal cell somata. These observations suggest that Zn2+ enhances GABA release from local circuit neurons that synapse onto pyramidal cell dendrites, and inhibits GABA release onto pyramidal cell somata.
Ricciardi
T N
TN
Department of Neurological Surgery, University of Washington, Seattle 98195, USA.
Malouf
A T
AT
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D046508:Culture Techniques; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D015032:Zinc