Circadian Clock Regulation of pH in the Rabbit Retina

Abstract

Although it is generally accepted that the acid-base ratio of tissue, as represented by the pH, is strictly regulated to maintain normal function, recent studies in the mammalian nervous system have shown that neuronal activity can result in significant shifts in pH. In the mammalian retina, many cellular phenomena, including neuronal activity, are regulated by a circadian clock. We thus investigated whether a clock regulates retinal pH, using pH-sensitive microelectrodes to measure the extracellular pH (pH o ) of the in vitro rabbit retina in the subjective day and night, that is, under conditions of constant darkness. These measurements demonstrated that a circadian clock regulates the pH o of the rabbit retina so that the pH o is lower at night than in the day. This day/night difference in retinal pH o was observed when the rabbits were maintained on a normal light/dark cycle and after they were maintained on a light/dark cycle that was phase-delayed by 9 hr. Continuous recordings of retinal pH o around subjective dusk indicated that the change from daytime to nighttime pH o is relatively fast and suggested that the clock that regulates pH o is located in the retina. The lowest pH o recorded in the retina in both the day and night was in the vicinity of the inner segments of photoreceptor cells, supporting the idea that photoreceptors serve as the primary source of protons. The circadian-induced shift in pH o was several times greater than light-induced pH o changes. These findings suggest that a circadian clock in the mammalian retina regulates retinal pH.

Coupling between A-Type Horizontal Cells Is Mediated by Connexin 50 Gap Junctions in the Rabbit Retina

“…Furthermore, the fluctuation of pH in the outer plexiform layer has a circadian rhythm (Dmitriev and Mangel, 2001). This suggests a possible mechanism whereby A-type HC coupling could also be regulated in a circadian cycle.…”

Retinal pH Reflects Retinal Energy Metabolism in the Day and Night

“…Extracellular pH in the retina was measured with double-barreled pH-selective microelectrodes based on the Hydrogen Ionophore ICocktail B (Fluka), as described previously (Dmitriev and Mangel 2001). The diameter of the microelectrode tip was ϳ5 m. The resistance of the pH-selective barrel was 5-10 GOhm, and the reference barrel had a resistance of 20 -50 MOhm.…”

Acid-Sensing Ion Channel 2 Is Important for Retinal Function and Protects against Light-Induced Retinal Degeneration

“…Protons that are coreleased with glutamate into photoreceptor ribbon synapses act as feedback inhibitors of Ca 2ϩ channels and thus transmitter release (Barnes et al, 1993;DeVries, 2001). Furthermore, the pH of the retina follows a circadian rhythm (Dmitriev and Mangel, 2001), and pH changes might play a role in the adaptation of the retinal responses to different light intensities. This led us to examine the presence and functional role of ASIC2 in the retina.…”