Intracellular calcium concentration rises have been reported following activation of GABA A receptors in neonatal preparations and attributed to activation of voltage-dependent Ca 2+ channels. However, we show that, in cerebellar interneurons, GABA A agonists induce a somatodendritic Ca 2+ rise that persists at least until postnatal day 20 and is not mediated by depolarization-induced Ca 2+ entry. A local Ca 2+ elevation can likewise be elicited by repetitive stimulation of presynaptic GABAergic afferent fibers. We find that, following GABA A receptor activation, bicarbonate-induced Cl - entry leads to cell depolarization, Cl - accumulation, and osmotic tension. We propose that this tension induces the intracellular Ca 2+ rise as part of a regulatory volume decrease reaction. This mechanism introduces an unexpected link between activation of GABA A receptors and intracellular Ca 2+ elevation, which could contribute to activity-driven synaptic plasticity.
Chavas, J., Forero, M. E., Collin, T., Llano, I., & Marty, A. (2004). Osmotic tension as a possible link between GABA A receptor activation and intracellular calcium elevation. Neuron, 44(4), 701–713. https://doi.org/10.1016/j.neuron.2004.11.002