Horizontal Cells Are Depolarized Following Both Prolonged Light and Dark Adaptation

Abstract

Purpose: : Following prolonged (>30 min) light adaptation, horizontal cells (HCs) contribute to ganglion cell surround responses (Mangel, 1991) possibly by releasing GABA onto bipolar cell dendrites, which express Cl^--permeable GABA_A receptors (GABA_ARs). If GABA_AR activation mediates the ON-bipolar cell surround, then HCs should release GABA under light-adapted conditions. However, it is commonly assumed that HCs, which hyperpolarize to light stimuli, are relatively hyperpolarized under light-adapted conditions due to reduced glutamate input from cones. Because HCs express greater levels of GABA_ARs and the Cl^- cotransporter Na-K-2Cl (NKCC), which mediates GABA-evoked depolarizations, following prolonged light adaptation, compared to prolonged dark adaptation (Cao et al., 2009, 2010, ARVO), we determined whether HCs are depolarized following both prolonged light and dark adaptation.

Methods: : The light responses and membrane potential of HCs in pigmented rabbits were compared following prolonged (>30 min) bright light (photopic) and dark (scotopic) adaptation without and during bath application of test drugs.

Results: : Thirty min of light adaptation, following 60 min of dark adaptation, depolarized HCs by ∼6 mV and decreased light response amplitudes. Slowly increasing the background illumination following 60 min of dark adaptation maintained HCs in a depolarized state. Bath application of picrotoxin, a GABA_A/C antagonist, or bumetanide, a selective inhibitor of NKCC activity, hyperpolarized HCs by ~22 mV vs. ~3 mV following prolonged light vs. dark adaptation, respectively.

Conclusions: : The results indicate that 1) the depolarized state of HCs is maintained during a gradual increase in background illumination and is similar following both prolonged light and dark adaptation and 2) NKCC and GABA_AR activity on HCs are greater following prolonged light adaptation compared to prolonged dark adaptation. Because the Cl^- conductance of HCs is ~3-fold greater than the glutamate-gated Na⁺ conductance (Yang et al., 1999), HCs may be dominated by a GABA-gated Cl^- conductance following light adaptation and a glutamate-gated Na⁺ conductance following dark adaptation, so that HCs remain in a depolarized state, releasing GABA, during the gradual changes in background illumination that normally occur throughout the day.

Keywords: horizontal cells • ion transporters • inhibitory receptors