Catsicas, M; Mobbs, P; (2001) GABA_{B} Receptors Regulate Chick Retinal Calcium Waves. Journal of Neuroscience , 21 (3) 897 - 910. 10.1523/JNEUROSCI.21-03-00897.2001.

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Abstract

Correlated spiking activity and associated Ca²⁺ waves in the developing retina are important in determining the connectivity of the visual system. Here, we show that GABA, via GABA_{B} receptors, regulates the temporal characteristics of Ca²⁺ waves occurring before synapse formation in the embryonic chick retina. Blocking ionotropic GABA receptors did no affect these Ca²⁺ transients. However, when these receptors were blocked, GABA abolished the transients, as did the GABA_{B} agonist baclofen. The action of baclofen was prevented by the GABA_{B} antagonistp-3-aminopropyl-p-diethoxymethyl phosphoric acid (CGP35348). CGP35348 alone increased the duration of the transients, showing that GABA_{B} receptors are tonically activated by endogenous GABA. Blocking the GABA transporter GAT-1 with 1-(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid (SKF89976A) reduced the frequency of the transients. This reduction was prevented by CGP35348 and thus resulted from activation of GABA_{B} receptors by an increase in external [GABA]. The effect of GABA_{B} receptor activation persisted in the presence of activators and blockers of the cAMP–PKA pathway. Immunocytochemistry showed GABA_{B} receptors and GAT-1 transporters on ganglion and amacrine cells from the earliest times when Ca²⁺ waves occur (embryonic day 8). Patch-clamp recordings showed that K⁺ channels on ganglion cell layer neurons are not modulated by GABA_{B} receptors, whereas Ca²⁺ channels are; however, Ca²⁺ channel blockade with ω-conotoxin-GVIA or nimodipine did not prevent Ca²⁺ waves. Thus, the regulation of Ca²⁺ waves by GABA_{B} receptors occurs independently of N- and L-type Ca²⁺ channels and does not involve K⁺ channels of the ganglion cell layer. GABA_{B} receptors are likely to be of key importance in regulating retinal development.

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