Potential contribution of a voltage-activated proton conductance to acid extrusion from rat hippocampal neurons

Cheng, Yen May; Kelly, T.; Church, John A.

doi:10.1016/j.neuroscience.2007.12.007

Cited by 22 publications

(21 citation statements)

References 63 publications

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“…No measureable voltage–gated proton current was detected, although, we recorded a current that may have been previously misidentified as a proton current 22 . This nonselective (E rev= 0) outward current was present in Hv1 −/− mice (Fig.…”

Section: Resultsmentioning

confidence: 90%

The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke

et al. 2012

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SUMMARYPhagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. Here we show that NOX–mediated damage can be inhibited by suppression of the voltage-gated proton channel, Hv1. Hv1 is required for full NOX activity since it compensates for loss of NOX–exported charge. We show that Hv1 is required for NOX–dependent ROS generation in brain microglia in situ and in vivo. Mouse and human brain microglia, but not neurons or astrocytes, express large Hv1-mediated currents. Mice lacking Hv1 were protected from NOX–mediated neuronal death and brain damage 24 hours after stroke. These results demonstrate that Hv1–dependent ROS production is responsible for a significant fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke.

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Section: Resultsmentioning

confidence: 90%

The voltage-gated proton channel Hv1 enhances brain damage from ischemic stroke

et al. 2012

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“…The activation of NMDA receptors induces a Ca 2+ dependent pH i acidification in rat HC neurons (Irwin et al, 1994) that is likely due to Ca-H exchange mediated by the Ca 2+ -ATPase (Makani and Chesler, 2010). The extent of the drop in neuronal pH i due to Ca 2+ -ATPase action during electrical activity is limited by a depolarization-induced alkalization that is likely mediated by the proton-efflux channel H V 1(Meech and Thomas, 1987; Cheng et al, 2008; Meech, 2012). Finally, we must not discount the contribution of acid-base transporters in the astrocytes (Chesler, 2003) and choroid plexus epithelia (Damkier et al, 2010a, 2013), cells that control the composition of the brain extracellular fluid and thus indirectly influence the pH of neurons.…”

Section: Neuronal Acid-base Transportersmentioning

confidence: 99%

Intracellular pH regulation by acid-base transporters in mammalian neurons

et al. 2014

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Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (JL) and extrusion (JE). The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3) and JE (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na+- coupled HCO3− transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions.

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“…Substantial evidence supports this function in a variety of cells. Recovery of pH by cells that are loaded with acid by HCl injection (211) or by the NH 4 + prepulse approach (176) is slowed by inhibiting proton channels with Zn 2+ in numerous cells (29, 59, 62, 110, 142, 150, 160, 164, 165, 194, 211). Depolarization by elevated [K + ] o to activate proton channels produces rapid alkalinization of TsA201 cells transfected with the murine proton channel, but not in non-transfected cells (184).…”

Section: Functions Of Voltage Gated Proton Channelsmentioning

confidence: 99%