GABAb receptors regulate chick retinal calcium waves.

Abstract

Correlated spiking activity and associated Ca(2+) 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 Ca(2+) waves occurring before synapse formation in the embryonic chick retina. Blocking ionotropic GABA receptors did no affect these Ca(2+) 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 Ca(2+) 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 Ca(2+) channels are; however, Ca(2+) channel blockade with omega-conotoxin-GVIA or nimodipine did not prevent Ca(2+) waves. Thus, the regulation of Ca(2+) waves by GABA(B) receptors occurs independently of N- and L-type Ca(2+) 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.

• Authors: M Catsicas, P Mobbs
• Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 21 Issue 3 Pg. 897-910 (Feb 01 2001) ISSN: 1529-2401 [Electronic] United States
• PMID: 11157076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Calcium Channels
• Carrier Proteins
• Fluorescent Dyes
• GABA Agents
• GABA Agonists
• GABA Antagonists
• GABA Plasma Membrane Transport Proteins
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• GABA-B Receptor Agonists
• GABA-B Receptor Antagonists
• Membrane Proteins
• Membrane Transport Proteins
• Nipecotic Acids
• Organic Anion Transporters
• Organic Chemicals
• Receptors, GABA-A
• Receptors, GABA-B
• calcium green
• gamma-Aminobutyric Acid
• N-(4,4-diphenyl-3-butenyl)nipecotic acid
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels (metabolism)
• Calcium Signaling (drug effects, physiology)
• Carrier Proteins (antagonists & inhibitors, metabolism)
• Chick Embryo
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Dose-Response Relationship, Drug
• Fluorescent Dyes
• GABA Agents (pharmacology)
• GABA Agonists (pharmacology)
• GABA Antagonists (pharmacology)
• GABA Plasma Membrane Transport Proteins
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• GABA-B Receptor Agonists
• GABA-B Receptor Antagonists
• In Vitro Techniques
• Membrane Proteins (antagonists & inhibitors, metabolism)
• Membrane Transport Proteins
• Nipecotic Acids (pharmacology)
• Organic Anion Transporters
• Organic Chemicals
• Patch-Clamp Techniques
• Receptors, GABA-A (metabolism)
• Receptors, GABA-B (metabolism)
• Retina (cytology, embryology, metabolism)
• Retinal Ganglion Cells (cytology, metabolism)
• Signal Transduction (drug effects, physiology)
• gamma-Aminobutyric Acid (metabolism, pharmacology)