Changes in the light-sensitive current of salamander rods upon manipulation of putative pH-regulating mechanisms in the inner and outer segment

Abstract

The light-sensitive current of dark-adapted rods isolated from the Ambystoma retina was recorded while either the inner or the outer segment (IS or OS) protruding from the suction pipette was exposed to treatments intended to reveal the physiological roles of pH-regulating transport mechanisms. Applied to the IS, both amiloride (presumed to block Na+/H+ exchange, 2 mM) and 4-4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) (presumed to block bicarbonate transport, 0.1 mM) generally abolished light sensitivity completely but reversibly, consistent with acidification of the IS. Yet, the circulating ("dark") current often persisted, implying that the OS was not acidified. Applied to the OS, amiloride depressed but DIDS increased the dark current and photoresponses. Given the fact that the current increases with rising OS-pHi, this suggests alkalinization, which could be due to DIDS inhibiting bicarbonate extrusion by HCO3-/Cl- exchangers in the OS. Consistent with this idea, replacing external Cl- by other anions increased the current as would be expected if HCO3-/Cl- exchange is reversed. We propose that the IS and OS manage their acid balances independently and with different sets of transport mechanisms. Acidosis in either compartment suppresses the photosensitivity of the rod, but by differing mechanisms.

Bicarbonate Modulates Photoreceptor Guanylate Cyclase (ROS-GC) Catalytic Activity

“…6D), similar to the findings of Ref. 26. Flash response kinetics in rods were unchanged or may have slowed slightly in low Cl Ϫ .…”

Therapeutic photobiomodulation for methanol-induced retinal toxicity

“…In addition, the amplitudes of the flicker ERG responses were significantly attenuated at all luminance intensities, achieving a maximal amplitude of 18 Ϯ 5 V, Ϸ28% of the maximum control response. These changes are indicative of a severe deficit in retinal function and are consistent with formateinduced inhibition of photoreceptor oxidative metabolism (6,7,(30)(31)(32). LED treatment significantly improved rod-and M-conemediated ERG responses in methanol-intoxicated rats.…”

“…At lower luminance intensities, LED treatment did not improve the ERG response in methanol-intoxicated rats, suggesting that the rate of activation of some components of phototransduction activation remained compromised by formate. Because the rate of activation of phototransduction depends on an adequate supply of GTP and ATP (30)(31)(32), it is possible that the formate-induced metabolic inhibition is only partly attenuated by our LED treatment protocol.…”

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

“…According to one study, ϳ28 M ATP per second and 126 M ATP per second are required for cGMP synthesis in the dark and after illumination, respectively (Ames et al, 1986). Both synthesis of cGMP from GTP and the hydrolysis of cGMP result in the generation of acid because of a net hydrolysis of an ester bond (Koskelainen et al, 1994). Thus local fluctuations in energy consumption, acid production, and extrusion between light and dark might be one mechanism that could create transient, localized pH changes around photoreceptors after light exposure.…”

“…ASIC2 channels desensitize after activation (Champigny et al, 1998) and are sensors for dynamic pH fluctuations rather than for static acidosis. Rods and cones are metabolically highly active and are the primary source of protons in the retina (Koskelainen et al, 1994). In the inner segments, energy metabolism produces lactic acid and CO 2 .…”