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The Journal of Neuroscience, February 1, 2001, 21(3):897-910

GABA_B Receptors Regulate Chick Retinal Calcium Waves

Marina Catsicas and Peter Mobbs

Department of Physiology, University College London, London WC1E 6BT, United Kingdom

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 antagonist p-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 -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.

Key words: retina; ganglion cells; Ca²⁺; spontaneous activity; GABA_B receptors; patch-clamping

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Copyright © 2001 Society for Neuroscience  0270-6474/01/213897-14$05.00/0

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