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

Abstract

Neurotransmitter release is known to be triggered by Ca¥ that enters presynaptic terminals through voltage-gated Ca¥ channels. Voltage-gated Ca¥ channels have been classified as T-, L_, N-, P-, Q-or R-type, depending on their voltage dependence, kinetic and pharmacological properties. A majority of electrophysiological reports suggest that high-threshold channels of the N-type in combination with P-type channels are responsible for transmitter release at central mammalian synapses (Horne & Kemp, 1991;Luebke, Dunlap & Turner, 1993;Takahashi & Momiyama, 1993;Ohno-Shosaku, Hirata, Sawada & Yamamoto, 1994;Regehr & Mintz, 1994;Mintz, Sabatini & Regehr, 1995;Poncer, McKinney, G ahwiler & Thompson, 1997). Involvement of Q-type channels (Wheeler, Randall & Tsien, 1994), and to a smaller extent L-type channels (Reuter, 1995), has also been suggested. In several of the above reports, the cells show a considerable homogeneity in the relative fraction of presynaptic Ca¥ influx that each channel type is responsible for. A few recent reports, however, have suggested a heterogeneous distribution of Ca¥ channel types in presynaptic terminals of the hippocampus (Reuter, 1995;Poncer et al. 1997;Reid, Clements & Bekkers, 1997). The medial preoptic nucleus (MPN) is possibly involved in several of the major functions ascribed to the preoptic area, such as control of sexual behaviour, thermoregulation, slowwave sleep and feeding. The inhibitory neurotransmitter ã_aminobutyric acid (GABA) has been suggested to be important for several of these functions. GABAergic synaptic contacts are widespread in the MPN, possibly forming local circuits in this region (Hoffman, Kim, Gorski & Dudek, 1994a 1. Voltage-dependent Ca¥ 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 ìÒ), showed a roughly unimodal amplitude distribution and a reversal potential consistent with a Cl¦ current, and were therefore attributed to GABAA receptors activated by synaptically released GABA. 3. Application of 140 mÒ 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 Ca¥-free solutions and showed a roughly hyperbolic relation to external Ca¥ concentration with half-saturation at 0·15 mÒ. They further depended on the concentration of applied KCl in a way expected for high-threshold Ca¥ channels. 4. The KCl-evoked synaptic currents were completely blocked by 200 ìÒ Cd¥, but only partially blocked by 200 ìÒ Ni¥. 5. The KCl-evoked synaptic currents were insensitive to the L-type Ca¥ channel blocker nifedipine (10 ìÒ). However, the synaptic currents were sensitive to either 1 ìÒ ù_conotoxin GVIA, 25 nÒ ù_agatoxin IVA or 1 ...

Allopregnanolone enhancement of GABAergic transmission in rat medial preoptic area neurons

“…In the present study, allopregnanolone failed to increase the mIPSC frequency in Ca 2ϩ -free external solution. This result suggests that external Ca 2ϩ is needed for allopregnanolone-facilitated release of GABA and appears to be in agreement with the reported triggering of GABA release from presynaptic nerve terminals in the MPOA by voltage-dependent calcium channels (VDCCs) in the active zone of synapses (8). Because of high Cl Ϫ concentration at the presynaptic nerve terminal (37), activation of presynaptic Cl Ϫ channels induces a Cl efflux, resulting in nerve terminal depolarization and Ca 2ϩ entry into nerve terminal through the VDCCs (12).…”

“…An increasing Ca 2ϩ concentration (8,12,17) may trigger neurotransmitter release. In the present study, allopregnanolone failed to increase the mIPSC frequency in Ca 2ϩ -free external solution.…”

Cholinergic neurotransmission in the preBÖtzinger Complex modulates excitability of inspiratory neurons and regulates respiratory rhythm

“…If this is the case, although our slice preparation does not contain the PTT/LDT, the remaining axons or terminals can still release ACh in the preBötC and XII nucleus as synaptic terminals and boutons can release neurotransmitters after they are isolated from cell bodies (Haage et al, 1998;Akaike and Moor-house, 2003). ACh may also be released from cholinergic neurons present locally in the rostral ventrolateral medulla (Jones, 1990;Ruggiero et al, 1990).…”

Contribution of Resting Conductance, GABAA-Receptor Mediated Miniature Synaptic Currents and Neurosteroid to Chloride Homeostasis in Central Neurons

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