Anoxia-evoked intracellular pH and Ca2+ concentration changes in cultured postnatal rat hippocampal neurons

Diarra, Abdoullah; Sheldon, Claire A.; Brett, Christopher L.; Baimbridge, K.G.; Church, John A.

doi:10.1016/s0306-4522(99)00230-4

Cited by 57 publications

(85 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Solutions containing Na 2 S 2 O 4 were prepared immediately before use and bubbled with either 100% Ar (HEPES-buffered media) or 5% CO 2 /95% Ar (HCO 3 Ϫ /CO 2 -buffered media); during perfusion with these media, the atmosphere in the recording chamber was switched to 100% Ar or 5% CO 2 /95% Ar, respectively. We have previously reported that media containing 1-2 mM Na 2 S 2 O 4 have P O2 values Ͻ1 mmHg and that the changes in pH i evoked by anoxia in rat hippocampal neurons are not secondary to any additional properties of the O 2 scavenger (Diarra et al, 1999;Sheldon and Church, 2002). In the present study, we assessed the possibility that Na 2 S 2 O 4 may induce changes in [Na ϩ ] i via mechanisms unrelated to its O 2 scavenging property in two ways.…”

Section: Methodsmentioning

confidence: 95%

“…affect the magnitudes of anoxia-induced increases in [Na ϩ ] i in neurons maintained for either 6 -10 or 11-14 DIV ( (Diarra et al, 1999) could activate forward-mode Na ϩ /Ca 2ϩ exchange and thereby contribute to Na ϩ influx, a rise in [Na ϩ ] i could promote reverse-mode operation of the exchanger and thus Na ϩ efflux. Forward-and reverse-mode operation of the plasmalemmal Na ϩ /Ca 2ϩ exchanger can be inhibited with bepridil (50 M) and KB-R7943 (1 M), respectively, whereas higher concentrations of KB-R7943 (10 M) inhibit both forward and reverse Na ϩ /Ca 2ϩ exchange in rat hippocampal neurons (Breder et al, 2000).…”

Section: Voltage-activated Namentioning

confidence: 99%

See 1 more Smart Citation

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sheldon

Diarra²,

Cheng³

et al. 2004

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

Mechanisms that contribute to Na ϩ influx during and immediately after 5 min anoxia were investigated in cultured rat hippocampal neurons loaded with the Na ϩ -sensitive fluorophore sodium-binding benzofuran isophthalate. -dependent mechanism(s). The results provide insight into the intrinsic mechanisms that contribute to disturbed internal Na ϩ homeostasis during and immediately after anoxia in rat hippocampal neurons and, in this way, may play a role in the pathogenesis of anoxic or ischemic cell injury.

show abstract

Section: Methodsmentioning

confidence: 95%

Section: Voltage-activated Namentioning

confidence: 99%

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sheldon

Diarra²,

Cheng³

et al. 2004

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, mild acidosis during less severe energy stress or seizure has been proposed to have protective effects by inhibiting the conductances of various pH-sensitive neurotransmitter-and voltage-gated ion channels (2-4, 83-85), thereby limiting Ca 2ϩ overload and damping membrane excitability associated with excitotoxicity, while at the same time permitting the gradual restoration of intra-and extracellular pH to resting values. With regard to the latter, Diarra et al (86) demonstrated that exposure of cultured postnatal rat hippocampal neurons to acute chemical anoxia induced a triphasic change in pH i consisting of an initial fall, subsequent rise, and further increase upon the return to normoxia, and implicated NHE activity as a contributing factor in the post-anoxic restoration of pH i . Our measurements of pH i in metabolically stressed cultured neonatal mouse hippocampal neurons complement and extend these earlier findings by showing that the gradual pH i recovery following acidification is likely dependent, at least in part, on AMPK and the recruitment/retention of NHE5 at the cell surface.…”

Section: Discussionmentioning

confidence: 99%

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

Jinadasa

Szabó

Numata

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Modest pH i changes have been observed under normal physiological conditions [e.g., changes of neuronal activity or the resting potential (5, 6)], and greater changes occur under pathological conditions such as hypoxia, ischemia, or epilepsy (4,7,8).…”

mentioning

confidence: 99%

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions

Palacios-Prado

Briggs

Skeberdis

et al. 2010

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

View full text Add to dashboard Cite

Intracellular pH (pH i ) can change during physiological and pathological conditions causing significant changes of electrical and metabolic cell-cell communication through gap junction (GJ) channels. In HeLa cells expressing wild-type connexin45 (Cx45) as well as Cx45 and Cx43 tagged with EGFP, we examined how pH i affects junctional conductance (g j ) and g j dependence on transjunctional voltage (V j ). To characterize V j gating, we fit the g j -V j relation using a stochastic four-state model containing one V j -sensitive gate in each apposed hemichannel (aHC); aHC open probability was a Boltzmann function of the fraction of V j across it. Using the model, we estimated gating parameters characterizing sensitivity to V j and number of functional channels. In homotypic Cx45 and heterotypic Cx45/Cx43-EGFP GJs, pH i changes from 7.2 to ∼8.0 shifted g j -V j dependence of Cx45 aHCs along the V j axis resulting in increased probability of GJ channels being in the fully open state without change in the slope of g j dependence on V j . In contrast, acidification shifted g j -V j dependence in the opposite direction, reducing open probability; acidification also reduced the number of functional channels. Correlation between the number of channels in Cx45-EGFP GJs and maximal g j achieved under alkaline conditions showed that only ∼4% of channels were functional. The acid dissociation constant (pK a ) of g j -pH i dependence of Cx45/Cx45 GJs was ∼7. The pK a of heterotypic Cx45/Cx43-EGFP GJs was lower, ∼6.7, between the pK a s of Cx45 and Cx43-EGFP (∼6.5) homotypic GJs. In summary, pH i significantly modulates junctional conductance of Cx45 by affecting both V j gating and number of functional channels.cell-cell coupling | pH-dependent gating | EGFP | hemichannel | connexon C hanges in intracellular pH (pH i ) take place under different physiological and pathological conditions, and H + ions have a broad effect on cell function including cell-cell electrical and metabolic communication mediated by gap junctions (GJs) and paracrine signaling through nonjunctional/unapposed hemichannels (1-4). Modest pH i changes have been observed under normal physiological conditions [e.g., changes of neuronal activity or the resting potential (5, 6)], and greater changes occur under pathological conditions such as hypoxia, ischemia, or epilepsy (4,7,8).During the last decade, significant progress has been made toward understanding the molecular mechanisms of pH-dependent modulation of GJs and hemichannels (2, 9-12). Several domains in the cytoplasmic loop and C terminus of connexin43 (Cx43) appear to be involved in pH-dependent gating (2, 9, 11, 12). Furthermore, pH-dependent interaction of connexins with other cytoplasmic proteins may be important in the remodeling of connexins and in protection from lesion spread after local ischemic injury (13,14).GJs provide channels with an inner diameter of ∼1.4 nm between the interiors of the coupled cells. This link allows the spread of electrical potential and small metabolites. Each GJ cha...

show abstract

Anoxia-evoked intracellular pH and Ca2+ concentration changes in cultured postnatal rat hippocampal neurons

Cited by 57 publications

References 74 publications

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Sodium Influx Pathways during and after Anoxia in Rat Hippocampal Neurons

Activation of AMP-activated Protein Kinase Regulates Hippocampal Neuronal pH by Recruiting Na+/H+ Exchanger NHE5 to the Cell Surface

pH-dependent modulation of voltage gating in connexin45 homotypic and connexin45/connexin43 heterotypic gap junctions

Contact Info

Product

Resources

About