Osmotic tension as a possible link between GABA(A) receptor activation and intracellular calcium elevation.
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
Joël
J
Laboratoire de Physiologie Cérébrale, CNRS UMR 8118, Université Paris 5, 45 rue des Saints Pères, 75006 Paris, France.
Forero
Maria Elisa
ME
Collin
Thibault
T
Llano
Isabel
I
Marty
Alain
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002531:Cerebellum / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D007395:Interneurons / Q000502:physiology*; D007424:Intracellular Fluid / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D009995:Osmosis / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology*
D018755:GABA Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D002118:Calcium