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bioRxiv · 10.1101/2020.06.29.178160

Unique actions of GABA arising from cytoplasmic chloride microdomains

Rahmati, N.·Normoyle, K. P.·Glykys, J.·Dzhala, V. I.·Lillis, K. P.·Kahle, K. T.·Raiyyani, R.·Jacob, T.·Staley, K. J.
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Abstract

Developmental, cellular, and subcellular variations in the direction of neuronal Cl- currents elicited by GABAA receptor activation have been frequently reported, and we found a corresponding variance in the reversal potential (EGABA) for individual interneurons synapsing on a single pyramidal cell. These findings suggest a corresponding variance in the cytoplasmic concentration of Cl- ([Cl-i]). We determined [Cl-]i by: 1) two-photon imaging of the Cl- sensitive, ratiometric fluorescent protein SuperClomeleon (sCLM); 2) Fluorescence Lifetime IMaging (FLIM) of the Cl- sensitive fluorophore MEQ; and 3) electrophysiological measurements of EGABA. These methods collectively demonstrated stable [Cl-]i microdomains in individual neurons in vivo. Fluorometric and electrophysiological estimates of local [Cl-]i were highly correlated. [Cl-]i microdomains persisted after pharmacological inhibition of cation-chloride cotransporters (CCCs) but steadily decreased after inhibiting the polymerization of the anionic macromolecule actin. These studies highlight the existence of functionally significant neuronal Cl- microdomains that modify the impact of GABAergic inputs.

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Rahmati, N., Normoyle, K. P., Glykys, J., Dzhala, V. I., Lillis, K. P., Kahle, K. T., Raiyyani, R., Jacob, T., Staley, K. J.. 2020-06-29. Unique actions of GABA arising from cytoplasmic chloride microdomains. https://doi.org/10.1101/2020.06.29.178160

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