Abstract
Abstract: :
Purpose: In goldfish, negative feedback from HCs to cones is GABA–independent and involves hemichannels present on the tips of the horizontal cell dendrites (Kamermans et al., 2001). Blocking hemichannels with either carbenoxolone or low concentrations of cobalt block the feedback–mediated responses in the outer retina. Since hemichannels are known to be very sensitive to intracellular changes in pH (Dixon et al., 1996;White et al., 1999;Ripps et al., 2002), we studied the effect of intracellular acidification on the feedback–mediated responses in both cones and HCs. Methods:Patch–clamp recordings of cones and voltage recordings of HCs in isolated goldfish retina. Results: Acetate–induced intracellular acidification inhibits the feedback–mediated responses in both cones and HCs. Unlike carbenoxolone or cobalt application, this inhibition is not coupled to HC hyperpolarization and a reduction of their light responses. In addition to the closure of hemichannels, Acetate directly modulates the calcium current of the cones. This direct effect of acetate on the calcium current of the cones prevents HCs to hyperpolarize severly in response to the block of the hemichannels, as is the case with carbenoxolone and cobalt. The result is that feedback is blocked with HCs still responding with almost normal response amplitude and without a change in resting membrane potential. Conclusions:The sensitivity of the feedback system to intracellular acidification confirms a role for hemichannels in negative feedback from HCs to cones.
Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • pharmacology • electrophysiology: non–clinical