Fast presynaptic GABAA receptor‐mediated Cl‐ conductance in cultured rat hippocampal neurones.

Abstract

1. Hippocampal neurones cultured from the 18-day-old embryonic rat for 3 days to 3 weeks were recorded with Cl--filled patch pipettes. Spontaneous synaptic currents, which reversed at the equilibrium potential for Cl-ions (Ec1) and were blocked by the GABAA (y-aminobutyric acid) receptor antagonists bicuculline or picrotoxin, were recorded in every culture. At 25°C and -80 mV they decayed with a time constant > 20 ms that invariably increased at positive potentials. After 2 weeks, 50-75% of all neurones were GABA immunoreactive. 2. In pairs-recordings, coincident synaptic currents in both cells were either spontaneous or evoked by stimulation of one cell. In the presence of tetrodotoxin and using pipettes containing lidocaine (lignocaine) N-ethyl bromide, coincident spontaneous Cl-transients still occurred in both neurones far more frequently than expected by chance. 3. Holding the potential of one neurone at a positive value reversed the synaptic transients in that cell and, in half of the cells, increased the frequency of coincident events in both cells. 4. In neurones where depolarization increased the frequency of coinciding events and all regenerative current apparent at the soma was abolished, short depolarizing pulses occasionally evoked all-or-none, pre-and postsynaptic currents with matching transmission failures and identical delays in transmission. 5. The results suggest that the same pulse of GABA simultaneously activates GABAA receptor-coupled Cl-channels on both sides of the same synaptic cleft, producing immediate auto-transmission in the absence of collaterals or interneurones.

Heterosynaptic expression of depolarization-induced suppression of inhibition (DSI) in rat hippocampal cultures

“…6E). If this type of transmission, called "cis-mission" (Vautrin et al 1994), contributes to the IACs recorded here, the decrease in GABA release in presynaptic terminals will also lead to the decrease in IAC amplitudes.…”

Subcellular localization of gamma-aminobutyric acid type A receptors is determined by receptor beta subunits.

“…(Bar = 15 ,um. ) cell bodies, and also axons (12)(13)(14)(15). How this differential receptor localization is achieved remains largely unknown.…”

“…Collectively, these studies have demonstrated that GABAA receptors can be found on dendrites, cell bodies, and axons (12)(13)(14)(15). To examine the potential role of receptor heterogeneity in controlling the subcellular targeting of GABAA receptors we have used heterologous expression of receptor cDNAs in Madin-Darby canine kidney (MDCK) cells.…”

Inhibition of GABA release by presynaptic ionotropic GABA receptors in hippocampal CA3

“…Ligandgated ion channels occur at many axon terminals [6], and may play a major role in short-term plasticity at excitatory synapses [17]. Ionotropic GABA receptors at mammalian axon terminals have been originally described by Eccles and co-workers [1] but are also present at various glycinergic [14], glutamatergic [18] and GABAergic [2][3][4] terminals. Depending on the direction and amplitude of the presynaptic potential change, such presynaptic GABA receptors may trigger [17] or suppress [5] antidromic action potentials, and can facilitate [2] or suppress [1] transmitter release.…”

“…It is well established that the central inhibitory transmitter GABA exerts such a negative feedback via presynaptic metabotropic GABA B autoreceptors. There is evidence, however, that GABA can also activate ionotropic autoreceptors in the mammalian spinal cord [1], retina [2], cerebellum [3] and in cultured hippocampal interneurons [4]. Recently, Ruiz and co-workers [5] have found that activation of GABA A receptors reduces action potential propagation and Ca 2 + entry at mossy fiber terminals.…”