GABAA receptor activation and the excitability of nerve terminals in the rat posterior pituitary.

Abstract

1. The activation of GABAA receptors in nerve terminal membranes gates a Cl-channel.Experiments were conducted to determine how the activation of this receptor influences membrane potentials, action potentials and voltage-activated Na+ and K+ channels.2. When activation of the GABAA receptor produced only conductance changes and no voltage changes, action potentials changed only slightly. The threshold for action potential generation increased by 15%. GABA reduced the broadening of action potentials caused by high frequency stimulation by only 7%. These results indicate that membrane shunting by GABA-gated Cl-channels plays a relatively minor role.3. By recording changes in the current through K+ channels in cell-attached patches, the activation of GABAA receptors was shown to depolarize the nerve terminal membrane from rest by 14 mV. The GABAB receptor agonist baclofen produced no change in resting membrane potential as measured by this same technique. 4. In whole-terminal recordings under current clamp, with pipettes containing various Clconcentrations, the GABA-induced depolarization increased with Ec.. 90 % of the Na+ channels and activated a small amount of K+ current. This suggests that inactivation of Na+ channels makes a major contribution to the inhibition of action potentials by GABA. 8. These results are consistent with the hypothesis that GABA inhibits neurosecretion by retarding impulse propagation into the terminal arborization. These results support a depolarization block mechanism for the inhibition of secretion, in which depolarization inactivates Na+ channels sufficiently to block action potentials.

Estimate of the Chloride Concentration in a Central Glutamatergic Terminal: A Gramicidin Perforated-Patch Study on the Calyx of Held

“…Second, in paired recordings, small depolarizations of the calyx facilitated release, but depolarizations positive to Ϫ60 mV produced varied effects, sometimes causing inhibition (Awatramani et al, 2005). Facilitation is caused by the weak activation of voltage-gated Ca 2ϩ channels and the subsequent small basal Ca 2ϩ increase (Awatramani et al, 2005); larger depolarizations inhibit release by inactivating Na ϩ and possibly Ca 2ϩ channels (Graham and Redman, 1994;Zhang and Jackson, 1995); in some systems the shunting of the action potential by the Cl Ϫ conductance is the primary mechanism of inhibition (Cattaert and El Manira, 1999). In the calyx, K ϩ conductances limit slow depolarizations from reaching the Cl Ϫ reversal potential.…”

“…The reverse argument is also true. (Zhang and Jackson, 1995) and retinal bipolar cell terminals (22 mM) (Billups and Attwell, 2002). Elevated [Cl Ϫ ] i is necessary for the depolarizing action of glycine or GABA.…”

Activation of Axonal Receptors by GABA Spillover Increases Somatic Firing

“…For example, tonic activation of presynaptic GABA A Rs modulates excitability of presynaptic terminals of the pituitary gland (Zhang and Jackson, 1995) and hippocampal mossy fibers (Ruiz et al, 2003). Other studies have shown that phasic changes in membrane potential at the calyx of Held spread back the axon, influencing AP generation up to 800 m away (Paradiso and Wu, 2009).…”

Coexistence of Excitatory and Inhibitory GABA Synapses in the Cerebellar Interneuron Network

“…In such recordings, however, effects of subthreshold depolarizations may still have been inhibitory because of depolarization-induced Na ϩ current inactivation or K ϩ current activation (Zhang and Jackson, 1995;Monsivais et al, 2000;Lu and Trussell, 2001). To address this issue, we tested how GPSPs would alter the postsynaptic excitability after a delay of 30 msec.…”

“…If the driving force E GABA -V m is negative, this hyperpolarizes the cell and inhibits its firing, except when hyperpolarization-induced excitatory conductances are activated, giving rise to rebound excitation [as in deep cerebellar nuclei (Llinas and Mühlethaler, 1988;Aizenman and Linden, 1999) or thalamic relay cells (Bal et al, 1995)]. Conversely, if the driving force is positive, the GPSP depolarizes the cell and is expected to increase its firing; however, the neuron can still be inhibited through shunting, as long as the GABA A conductances are active (Staley and Mody, 1992;Gao et al, 1998), or through longer-lasting, depolarization-induced Na ϩ channel inactivation (Zhang and Jackson, 1995) or K ϩ channel activation (Monsivais et al, 2000).…”