GABA Provides a Swell Route to Calcium

Science's STKE  23 Nov 2004:
Vol. 2004, Issue 260, pp. tw420
DOI: 10.1126/stke.2602004tw420

In addition to its role as neurotransmitter, γ-aminobutyric acid (GABA) mediates trophic effects during neuronal development. These long-term actions have been hypothesized to depend on Ca2+ influx through voltage-dependent Ca2+ channels, a consequence of activation of GABAA receptors (ligand-gated ion channels that are permeable to Cl and HCO3), which can lead to depolarization in developing neurons. Chavas et al. loaded interneurons in cerebellar slices from juvenile rats with a calcium indicator and observed that application of the GABA agonist muscimol elicited a rise in [Ca2+]i, which was greater in dendrites than in the cell body. The authors used cell-attached recordings in which they measured currents through single BK channels to simultaneously evaluate membrane potential and [Ca2+]i, and they observed that a late phase of increased [Ca2+]i did not correlate with membrane depolarization. Moreover, the [Ca2+]i increase was not blocked by cadmium, and the threshold for calcium channel activation was higher than the peak depolarization in response to muscimol. Both changes in membrane potential and changes in [Ca2+]i required HCO3; the late phase of increased [Ca2+]i was inhibited by ryanodine. Dendrites expanded in size during muscimol application, and hypoosmotic solutions mimicked, whereas hyperosmotic solutions inhibited, the [Ca2+]i response to muscimol. Thus, the authors proposed that the rise in [Ca2+]i thatoccurs following GABAA receptor activation depends on increased osmotic tension following bicarbonate-dependent influx of Cl. The sensitivity to ryanodine suggested that this might involve release of Ca2+ from intracellular stores, linking ion flux through a ligand-gated channel to a metabotropic receptor-like response.

J. Chavas, M. E. Forero, T. Collin, I. Llano, A. Marty, Osmotic tension as a possible link between GABAA receptor activation and intracellular calcium elevation. Neuron 44, 701-713 (2004). [Online Journal]