Intracellular calcium ions decrease the affinity of the GABA receptor

Abstract

Intracellular free Ca2+ [( Ca2+]i) plays a crucial role in the transduction of extracellular signals. It has been implicated in the modulation of light sensitivity in Limulus photoreceptors and in the efficacy of synaptic transmission; calcium ion fluxes are also involved in the postsynaptic facilitation of nicotinic transmission seen in sympathetic ganglia, and in activation of the acetylcholine (ACh) receptor. [Ca2+]i is also a second messenger for many biologically active substances. We recorded neuronal activities of sensory neurones from the bullfrog (Rana catesbiana), using the suction pipette method and a 'concentration clamp' technique to apply gamma-aminobutyric acid (GABA) to the cell. We report the first evidence that [Ca2+]i suppresses the GABA-activated Cl- conductance, by decreasing the apparent affinity of the GABA receptor.

GABAA receptor function is regulated by phosphorylation in acutely dissociated guinea‐pig hippocampal neurones.

“…Increases in [Ca2+]i reduced the open time of GABAA receptor channels in pituitary cells (Taleb, Trouslard, Demeneix, Feltz, Bossu, Dupont & Feltz, 1987). In bull-frog sensory neurones (Inoue, Oomura, Yakushiji & Akaike, 1986) elevation of [Ca2+]i decreased the GABAA response by altering the binding affinity of GABA receptors. It is as yet unclear whether the run-down of the GABA response in CAI pyramidal cells occurs as a result of a decrease in receptor affinity for GABA or because of an inactivation of the GABA receptor.…”

Sequential Release of GABA by Exocytosis and Reversed Uptake Leads to Neuronal Swelling in Simulated Ischemia of Hippocampal Slices

“…entry through NMDA receptors Since glutamate released after the AD activates NMDA receptors (Rossi et al, 2000) and Ca 2ϩ entry through NMDA receptors is known to reduce the activity of GABA A receptors (Inoue et al, 1986;Stelzer and Shi, 1994;Chen and Wong, 1995), we were interested in whether inactivation of GABA A receptors after the AD might explain the lack of effect of GABAzine on swelling 5 min after the AD (Fig. 7E).…”

Effects of diuretics on GABA‐gated chloride current in frog isolated sensory neurones

“…Recently, we have recorded the GABA-gated Ic, in frog isolated sensory neurones using a 'concentration-clamp' technique under voltage-clamp conditions and studied the pharmacological and electrical properties of the GABA response (Hattori et al, 1984;Ishizuka et al, 1984;Akaike et al, 1985;Inoue et al, 1986). The newly developed 'concentration-clamp' technique combines internal perfusion with a modified suction pipette technique (Hattori et al, 1984;Ishizuka et al, 1984); rapid solution change within a few ms in the cellattached condition provides a reliable and efficient means of studying the kinetics of agonist-induced ionic currents even in the activation phase .…”