An EAAT2b/SLC1A2b-mediated chloride leak current enables rapid cone photoreceptor signalling

TL;DR

A specific chloride current in zebrafish cone photoreceptors, mediated by EAAT2b, supports rapid visual signaling and is crucial for processing fast visual stimuli.

Contribution

The study identifies a novel chloride leak current in cone photoreceptors mediated by EAAT2b, revealing a new functional role for excitatory amino acid transporters.

Findings

EAAT2b knockout zebrafish showed reduced electroretinogram b-wave amplitudes.

EAAT2b-deficient larvae exhibited impaired temporal processing of visual stimuli.

EAAT2b-mediated chloride current stabilizes cone resting membrane potential for rapid signaling.

Abstract

Excitatory amino acid transporters not only mediate high-affinity glutamate uptake but also conduct an uncoupled chloride current. In zebrafish, a whole-genome duplication gave rise to two eaat2 paralogues with distinct roles. Excitatory amino acid transporter 2a (SLC1A2b, GLT-1) functions primarily in Müller glia as a glutamate transporter, whereas excitatory amino acid transporter 2b is expressed in cone photoreceptors and exhibits a prominent glutamate-independent chloride current. We hypothesized that this leak current stabilizes the cone resting membrane potential, thereby supporting rapid visual signalling. In order to test this hypothesis, we generated eaat2b knockout zebrafish using CRISPR-Cas9-mediated genome editing. While eaat2b mutants showed no gross morphological abnormalities, they exhibited reduced electroretinogram b-wave amplitudes. Consistent with our hypothesis, eaat2b-deficient larvae displayed a significant reduction in flicker fusion electroretinogram power at each stimulus frequency, indicating impaired temporal processing likely due to delayed repolarization of cone photoreceptors. Our findings reveal a critical role for an excitatory amino acid transporter 2b-mediated chloride anion leak current in regulating the kinetics of photoreceptor responses. This functional innovation, enabled by a whole-genome duplication in the teleost lineage, highlights how gene duplications can lead to the acquisition of physiologically relevant new functions.

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