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Heterogeneous presynaptic Ca²⁺ channel types triggering GABA release onto medial preoptic neurons from rat

David Haage *, Urban Karlsson ¹ and Staffan Johansson *

1. Voltage-dependent Ca²⁺ channels triggering GABA release onto neurons from the medial preoptic nucleus of rat were investigated. Acutely dissociated neurons with adherent functional synaptic terminals were investigated by tight-seal whole-cell recordings from the postsynaptic cells.

2. Spontaneous current events similar to miniature postsynaptic currents were recorded. They were blocked by bicuculline (100 µM), showed a roughly unimodal amplitude distribution and a reversal potential consistent with a Cl^- current, and were therefore attributed to GABA_A receptors activated by synaptically released GABA.

3. Application of 140 mM KCl, expected to depolarize presynaptic terminals, evoked currents that were ascribed to a more massive release of GABA. The KCl-induced synaptic currents were abolished in Ca²⁺-free solutions and showed a roughly hyperbolic relation to external Ca²⁺ concentration with half-saturation at 0·15 mM. They further depended on the concentration of applied KCl in a way expected for high-threshold Ca²⁺ channels.

4. The KCl-evoked synaptic currents were completely blocked by 200 µM Cd²⁺, but only partially blocked by 200 µM Ni²⁺.

5. The KCl-evoked synaptic currents were insensitive to the L-type Ca²⁺ channel blocker nifedipine (10 µM). However, the synaptic currents were sensitive to either 1 µM -conotoxin GVIA, 25 nM -agatoxin IVA or 1 µM -conotoxin MVIIC.

6. It was concluded that, in many presynaptic terminals, the Ca²⁺ influx triggering GABA release onto medial preoptic neurons is mainly mediated by one predominant type of high- threshold Ca²⁺ channel that may be either of N-, P- or Q-type.

7. It was further concluded that terminals with similar predominant channel types often were clustered on the same postsynaptic cell.

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