GABABReceptors Regulate Chick Retinal Calcium Waves

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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 GABAB 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 GABAB agonist baclofen. The action of baclofen was prevented by the GABAB antagonistp-3-aminopropyl-p-diethoxymethyl phosphoric acid (CGP35348). CGP35348 alone increased the duration of the transients, showing that GABAB 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 GABAB receptors by an increase in external [GABA]. The effect of GABAB receptor activation persisted in the presence of activators and blockers of the cAMP–PKA pathway. Immunocytochemistry showed GABAB 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 GABAB 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 GABAB receptors occurs independently of N- and L-type Ca2+ channels and does not involve K+ channels of the ganglion cell layer. GABAB receptors are likely to be of key importance in regulating retinal development.