The effects of acetazolamide in albino rabbits, pigmented rabbits, and humans

Odom, J. Vernon; Nork, T. Michael; Schroeder, Barbara M.; Cavender, S; Slycken, Steven Van; Leys, Monique

doi:10.1016/0042-6989(94)90220-8

Cited by 10 publications

(2 citation statements)

References 12 publications

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“…The smaller increase in bicarbonate induced circulating current with acetazolamide in IS-in recordings meant that cones produced bicarbonate internally from CO 2 in equilibrium with bicarbonate in aqueous solution. These results help to account for the reduced photopic a-wave of the mammalian ERG particularly with bright flashes on administration of carbonic anhydrase inhibitor (Broeders et al, 1988; Odom et al, 1994; Sauvé et al, 2006) and indicate that it was not just due to acidosis. Dorzolamide inhibited recombinant murine carbonic anhydrase II in COS cells (Fig.…”

Section: Discussionmentioning

confidence: 79%

Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones

Makino

Duda

Pertzev

et al. 2019

eNeuro

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The membrane guanylate cyclase, ROS-GC, that synthesizes cyclic GMP for use as a second messenger for visual transduction in retinal rods and cones, is stimulated by bicarbonate. Bicarbonate acts directly on ROS-GC1, because it enhanced the enzymatic activity of a purified, recombinant fragment of bovine ROS-GC1 consisting solely of the core catalytic domain. Moreover, recombinant ROS-GC1 proved to be a true sensor of bicarbonate, rather than a sensor for CO2. Access to bicarbonate differed in rods and cones of larval salamander, Ambystoma tigrinum, of unknown sex. In rods, bicarbonate entered at the synapse and diffused to the outer segment, where it was removed by Cl--dependent exchange. In contrast, cones generated bicarbonate internally from endogenous CO2 or from exogenous CO2 that was present in extracellular solutions of bicarbonate. Bicarbonate production from both sources of CO2 was blocked by the carbonic anhydrase inhibitor, acetazolamide. Carbonic anhydrase II expression was verified immunohistochemically in cones but not in rods. In addition, cones acquired bicarbonate at their outer segments as well as at their inner segments. The multiple pathways for access in cones may support greater uptake of bicarbonate than in rods and buffer changes in its intracellular concentration.

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Section: Discussionmentioning

confidence: 79%

Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones

Makino

Duda

Pertzev

et al. 2019

eNeuro

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“…Through a unique Ca 2+ -independent mechanism, ROS-GC catalytic activity is stimulated by bicarbonate to provide for an increase in circulating current, quickened flash responses, and reduced relative sensitivity (Duda et al, 2015 ). These bicarbonate effects may for the first time explain the observed larger photoreceptor response in the ERG of the isolated retina treated with bicarbonate (Donner et al, 1990 ; Koskelainen et al, 1993 ) or the reduced photoreceptor response in the ERGs of human subjects and animal models treated with carbonic anhydrase inhibitors (Broeders et al, 1988 ; Odom et al, 1994 ; Findl et al, 1995 ).…”

Section: Introductionmentioning

confidence: 98%

Bicarbonate and Ca2+ Sensing Modulators Activate Photoreceptor ROS-GC1 Synergistically

Duda

Pertzev

Makino

et al. 2016

Front. Mol. Neurosci.

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Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca2+ levels are low. In cones, the additional expression of the Ca2+-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca2+ levels. Independent of Ca2+, ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain (CCD). Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca2+-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F514S mutation in ROS-GC1 that causes blindness in type 1 Leber’s congenital amaurosis (LCA) severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca2+ signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F514S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca2+. Our study challenges the recently proposed GCAP1 and GCAP2 “overlapping” phototransduction model (Peshenko et al., 2015b).

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Treatment with Carbonic Anhydrase Inhibitors Depresses Electroretinogram Responsiveness in Mice

Sauvé¹,

Karan²,

Yang³

et al.

Retinal Degenerative Diseases

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The effects of acetazolamide in albino rabbits, pigmented rabbits, and humans

Cited by 10 publications

References 12 publications

Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones

Modes of Accessing Bicarbonate for the Regulation of Membrane Guanylate Cyclase (ROS-GC) in Retinal Rods and Cones

Bicarbonate and Ca2+ Sensing Modulators Activate Photoreceptor ROS-GC1 Synergistically

Treatment with Carbonic Anhydrase Inhibitors Depresses Electroretinogram Responsiveness in Mice

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