Carbonic anhydrase in primary sensory neurons of dorsal root ganglia

Kazimierczak, J

doi:10.1016/0305-0491(87)90233-1

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…Whether this represents the CA activity described in this report is unclear, since this enzyme might be largely associated with intracellular organelles (30,50). In dorsal root ganglia, there is ultrastructural evidence for extracellular CA on neurons (51), but there is no data regarding cellular localization in the extracellular space of the central nervous system. This issue could have significant functional implications, since local activity of CA could determine the magnitude and time course of the pH transients arising from synaptic transmission.…”

Section: B Aphomentioning

confidence: 74%

pH transients evoked by excitatory synaptic transmission are increased by inhibition of extracellular carbonic anhydrase.

Chen

Chesler

1992

Proc. Natl. Acad. Sci. U.S.A.

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December 19, 1991) ABSTRACT Excitatory synaptic transmission has been associated with a rapid alkalinition of the brain extracellular space. These pH shifts are markedly increased by acetazolamide, an inhibitor of carbonic anhydrase. Although this effect can be readily explained by inhibition of extracellular carbonic anhydrase, this enzyme has been considered strictly intracellular in the central nervous system. To determine whether these alkaline shifts are regulated by extracellular carbonic anhydrase, we studied the effects of a membrane impermeant, dextran-bound inhibitor of this enzyme. Extraceflular alkaline transients, measured with pH-sensitive microelectrodes, were generated in the CAl region of rat hippocampal slices by repetitive electrical stimulation of Schaeffer collateral fibers or by local ejection of glutamate. More direct lkalinizations were elicited by focal ejection of NaOH in the vicinity of a pH microelectrode. These pH transients were reversibly enhanced by addition of the dextran-bound inhibitor. We conclude that there is significant carbonic anhydrase activity in the extracellular space of the brain. We postulate that this enzyme functions in the regulation and modulation of extracellular pH transients associated with neuronal activity.The enzyme carbonic anhydrase (CA) catalyzes the reversible hydration of CO2 and plays an important role in the function of erythrocytes and secretory epithelia (1). In the central nervous system, CA is abundant (2) and has been localized predominantly within glia (3-5) and choroid plexus (6). However, apart from its role in the secretion of cerebral spinal fluid (7,8), the functions of CA in the brain have remained obscure.While most forms of CA are intracellular, an extracellular isoform exists in several tissues, including kidney, lung, and muscle (9). Although there is no morphological evidence for extracellular CA in the brain, inhibitors of CA have been shown to have a large effect on the behavior of extracellular pH. Sulfonamide derivatives, such as acetazolamide, greatly increased the alkaline shifts associated with synaptic transmission (10-13). These effects could not be explained by enhancement of electrophysiological responses, since corresponding field potentials were unaffected. However, it remained unclear whether the action of acetazolamide was principally intracellular or extracellular, as this agent can readily penetrate cell membranes (1).It was subsequently noted that the effects of acetazolamide could be simply explained by a decrease in the extracellular buffering capacity (14). Experimental manipulation of the extracellular buffering power supported this view: synaptically evoked alkaline shifts were enhanced when bicarbonatebuffered saline was replaced by poorly buffered solutions containing Hepes (15,16). Although a role of metabolically generated CO2 could not be ruled out, the amplification and persistence of these alkalinizations in Hepes-buffered media suggested that shifts in CO2 and bicarbonate were not immediately respo...

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Section: B Aphomentioning

confidence: 74%

pH transients evoked by excitatory synaptic transmission are increased by inhibition of extracellular carbonic anhydrase.

Chen

Chesler

1992

Proc. Natl. Acad. Sci. U.S.A.

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“…These features suggested that CA XIV might be the extracellular CA that had been postulated to explain the effects of CA inhibitors in enhancing the extracellular alkaline shift after synaptic transmission (13,14). Histochemical evidence had also suggested a CA activity on surfaces of neuronal cell bodies and axons (21), but no prior immunologic reagent had identified such an activity.…”

Section: Discussionmentioning

confidence: 99%

Expression of membrane-associated carbonic anhydrase XIV on neurons and axons in mouse and human brain

Parkkila

Rajaniemi

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

116

105

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Although long suspected from histochemical evidence for carbonic anhydrase (CA) activity on neurons and observations that CA inhibitors enhance the extracellular alkaline shifts associated with synaptic transmission, an extracellular CA in brain had not been identified. A candidate for this CA was suggested by the recent discovery of membrane CA (CA XIV) whose mRNA is expressed in mouse and human brain and in several other tissues. For immunolocalization of CA XIV in mouse and human brain, we developed two antibodies, one against a secretory form of enzymatically active recombinant mouse CA XIV, and one against a synthetic peptide corresponding to the 24 C-terminal amino acids in the human enzyme. Immunostaining for CA XIV was found on neuronal membranes and axons in both mouse and human brain. The highest expression was seen on large neuronal bodies and axons in the anterolateral part of pons and medulla oblongata. Other CA XIV-positive sites included the hippocampus, corpus callosum, cerebellar white matter and peduncles, pyramidal tract, and choroid plexus. Mouse brain also showed a positive reaction in the molecular layer of the cerebral cortex and granular cellular layer of the cerebellum. These observations make CA XIV a likely candidate for the extracellular CA postulated to have an important role in modulating excitatory synaptic transmission in brain.

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“…In the nervous system, in contrast, there has been little morphological evidence of extracellular CA. Histochemical studies suggested the presence of interstitial CA in dorsal root ganglia (106); however, such methods did not allow definitive extracellular localization. The physiological demonstration of extracellular CA in hippocampal slices (71,72,150) nearly coincided with immunocytochemical studies of brain using antibodies against CA type IV.…”

Section: Nature Of Interstitial Ca Activity In Brainmentioning

confidence: 96%

Regulation and Modulation of pH in the Brain

Chesler

2003

Physiological Reviews

771

777

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The regulation of pH is a vital homeostatic function shared by all tissues. Mechanisms that govern H+ in the intracellular and extracellular fluid are especially important in the brain, because electrical activity can elicit rapid pH changes in both compartments. These acid-base transients may in turn influence neural activity by affecting a variety of ion channels. The mechanisms responsible for the regulation of intracellular pH in brain are similar to those of other tissues and are comprised principally of forms of Na+/H+ exchange, Na+-driven Cl-/HCO3- exchange, Na+-HCO3- cotransport, and passive Cl-/HCO3- exchange. Differences in the expression or efficacy of these mechanisms have been noted among the functionally and morphologically diverse neurons and glial cells that have been studied. Molecular identification of transporter isoforms has revealed heterogeneity among brain regions and cell types. Neural activity gives rise to an assortment of extracellular and intracellular pH shifts that originate from a variety of mechanisms. Intracellular pH shifts in neurons and glia have been linked to Ca2+ transport, activation of acid extrusion systems, and the accumulation of metabolic products. Extracellular pH shifts can occur within milliseconds of neural activity, arise from an assortment of mechanisms, and are governed by the activity of extracellular carbonic anhydrase. The functional significance of these compartmental, activity-dependent pH shifts is discussed.

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Carbonic anhydrase in primary sensory neurons of dorsal root ganglia

Cited by 9 publications

References 24 publications

pH transients evoked by excitatory synaptic transmission are increased by inhibition of extracellular carbonic anhydrase.

pH transients evoked by excitatory synaptic transmission are increased by inhibition of extracellular carbonic anhydrase.

Expression of membrane-associated carbonic anhydrase XIV on neurons and axons in mouse and human brain

Regulation and Modulation of pH in the Brain

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