Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal CA1 neurones

Smith, Garth A. M.; Brett, Christopher L.; Church, John A.

doi:10.1111/j.1469-7793.1998.487be.x

Cited by 39 publications

(68 citation statements)

References 48 publications

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“…Specifically, these researchers have suggested that manic and depressive states may be at least partially caused by the brain's attempts to correct this pH imbalance by causing an overactivation of monoaminergic systems, which has been known to increase pHi at least in hippocampal neurons. 53 Such a theory would also thus explain the more normalized pHi of bipolar patients in the manic and depressive states. 52 …”

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confidence: 99%

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

2005

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Magnetic resonance spectroscopy (MRS) affords a noninvasive window on in vivo brain chemistry and, as such, provides a unique opportunity to gain insight into the biochemical pathology of bipolar disorder. Studies utilizing proton ( 1 H) MRS have identified changes in cerebral concentrations of N-acetyl aspartate, glutamate/glutamine, choline-containing compounds, myo-inositol, and lactate in bipolar subjects compared to normal controls, while studies using phosphorus ( 31 P) MRS have examined additional alterations in levels of phosphocreatine, phosphomonoesters, and intracellular pH. We hypothesize that the majority of MRS findings in bipolar subjects can be fit into a more cohesive bioenergetic and neurochemical model of bipolar illness that is both novel and yet in concordance with findings from complementary methodological approaches. In this review, we propose a hypothesis of mitochondrial dysfunction in bipolar disorder that involves impaired oxidative phosphorylation, a resultant shift toward glycolytic energy production, a decrease in total energy production and/or substrate availability, and altered phospholipid metabolism. Molecular Psychiatry (2005) 10, 900-919.

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confidence: 99%

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

2005

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“…BCECF-derived fluorescence emission intensities during excitation at 488 nm and 452 nm were at least 20-fold higher than the original GFP fluorescence signal. The dual excitation ratio method was used to estimate pH i employing a fluorescence ratio-imaging system (Atto Biosciences, Rockville, MD); full details of the methods employed have been presented previously (52,53). The high-[K ϩ ]/nigericin technique was employed to convert background-corrected BCECF emission intensity ratios into pH i values.…”

Section: Namentioning

confidence: 99%

“…Intracellular acid loads were imposed by exposing the cells for 2 min to NH 4 ϩ -choline solution. The recovery of pH i following an NH 4 ϩ pre-pulse was fitted to a single exponential function, and the first derivative of this function was used to determine the rate of change of pH i (dpH i /dt) at 0.05 pH i unit increments from the point of maximum acidification (52,53). Proton efflux was calculated by multiplying the measured dpH i /dt at a given pH i value by the intrinsic intracellular buffering capacity (␤ i ) at the same pH i value.…”

Section: Namentioning

confidence: 99%

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Diering

Church

Numata

2009

Journal of Biological Chemistry

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NHE5 is a brain-enriched Na ؉ /H؉ exchanger that dynamically shuttles between the plasma membrane and recycling endosomes, serving as a mechanism that acutely controls the local pH environment. In the current study we show that secretory carrier membrane proteins (SCAMPs), a group of tetraspanning integral membrane proteins that reside in multiple secretory and endocytic organelles, bind to NHE5 and co-localize predominantly in the recycling endosomes. In vitro protein-protein interaction assays revealed that NHE5 directly binds to the N-and C-terminal cytosolic extensions of SCAMP2. Heterologous expression of SCAMP2 but not SCAMP5 increased cell-surface abundance as well as transporter activity of NHE5 across the plasma membrane. Expression of a deletion mutant lacking the SCAMP2-specific N-terminal cytosolic domain, and a mini-gene encoding the N-terminal extension, reduced the transporter activity. Although both Arf6 and Rab11 positively regulate NHE5 cell-surface targeting and NHE5 activity across the plasma membrane, SCAMP2-mediated surface targeting of NHE5 was reversed by dominant-negative Arf6 but not by dominant-negative Rab11. Together, these results suggest that SCAMP2 regulates NHE5 transit through recycling endosomes and promotes its surface targeting in an Arf6-dependent manner.

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“…It is expected that other channels or exchangers mediating cellular pH i changes could also give rise to relatively large pH i shifts beneath the plasma membrane. There is also potential for the feedback stimulation of pH regulatory mechanisms as a consequence of raised local cAMP levels (6,43,44) or the functional coupling of G protein-linked receptors to AC and acid extruders via divergent signaling mechanisms (45 Very significantly, however, we were able to prove that NHE1 was localized to the same subcellular compartments (caveolae) that expressed high levels of functional AC8. A similar distribution of NHE1 was also observed in membrane fractions from C6-2B glioma cells.…”

Section: Nhe1 Activity Protects Ac8 From Local Acid Shifts In Hek 293mentioning

confidence: 80%

“…However, it is now recognized that modest fluctuations in pH i can arise during "physiological" cellular activity (1)(2)(3)(4)(5)(6)(7)(8)(9). Furthermore, recent studies have provided evidence for pH i microdomains just beneath the plasma membrane, which can exhibit transient pH shifts on the order of several tenths of a pH unit, as a consequence of the local activity of plasma membrane transporters (10 -12).…”

Section: Intracellular Ph (Ph I )mentioning

confidence: 99%

Localized Na+/H+ Exchanger 1 Expression Protects Ca2+-regulated Adenylyl Cyclases from Changes in Intracellular pH

Willoughby

Masada

Crossthwaite

et al. 2005

Journal of Biological Chemistry

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The Ca 2؉ -sensitive adenylyl cyclases (ACs) are exclusively regulated by capacitative Ca 2؉ entry (CCE) in nonexcitable cells. The present study investigates whether this Ca 2؉ -dependent modulation of AC activity is further regulated by local pH changes that can arise beneath the plasma membrane as a consequence of cellular activity. Ca 2؉ stimulation of AC8 expressed in HEK 293 cells and inhibition of endogenous AC6 in C6-2B glioma cells exhibited clear sensitivity to modest pH changes in vitro. Acid pH (pH 7.14) reduced the Ca 2؉ sensitivity of both ACs, whereas alkaline pH (pH 7.85) enhanced the responsiveness of the enzymes to Ca 2؉ , compared with controls (pH 7.50). Surprisingly, in the intact cell, the response of AC8 and AC6 to CCE was largely unperturbed by similar changes in intracellular pH (pH i ), imposed using a weak acid (propionate) or weak base (trimethylamine). A range of hypotheses were tested to identify the mechanism(s) that could underlie this lack of pH effect in the intact cell. The pH sensitivity of CCE in HEK 293 cells is likely to dampen the effects of pH i on Ca 2؉ -regulated ACs and may partly explain the discrepancy between in vitro and in vivo data. However, we have found that the Na ؉ /H ؉ exchanger (NHE), NHE1, is functionally active in these cells, and like AC8 (and AC6) it resides in lipid rafts or caveolae, which may create cellular microdomains where pH i is tightly regulated. An abundance of NHE1 in these cellular subdomains may generate a privileged environment that protects the Ca 2؉ -sensitive ACs and other caveolar proteins from local acid shifts. Intracellular pH (pH i )1 is a fundamental determinant of cell function that, until recently, was considered to be tightly regulated due to rapid H ϩ diffusion, buffering, and ion transport mechanisms. However, it is now recognized that modest fluctuations in pH i can arise during "physiological" cellular activity (1-9). Furthermore, recent studies have provided evidence for pH i microdomains just beneath the plasma membrane, which can exhibit transient pH shifts on the order of several tenths of a pH unit, as a consequence of the local activity of plasma membrane transporters (10 -12). Fluctuations of [H ϩ ] within these microdomains could potentially exert profound effects on the numerous cellular proteins residing within or near the plasma membrane, including the cAMP-producing adenylyl cyclase (AC). Early in vitro studies of plasma membrane preparations demonstrated that the catalytic activity of AC is steeply pH-dependent, over the range of pH 6.0 -8.5, where acidification or alkalinization, respectively, decreases or increase cAMP synthesis (13-15).In addition to the pH dependence of AC catalytic activity, the Ca 2ϩ sensitivity of the Ca 2ϩ -regulated ACs is also likely to be highly pH-sensitive. Four of the nine AC isoforms cloned to date are regulated by submicromolar concentrations of Ca 2ϩ . AC1 and AC8 are stimulated by Ca 2ϩ acting via calmodulin, whereas AC5 and AC6 are inhibited, independently of calmodulin (16)...

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Effects of noradrenaline on intracellular pH in acutely dissociated adult rat hippocampal CA1 neurones

Cited by 39 publications

References 48 publications

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research

Secretory Carrier Membrane Protein 2 Regulates Cell-surface Targeting of Brain-enriched Na+/H+ Exchanger NHE5

Localized Na+/H+ Exchanger 1 Expression Protects Ca2+-regulated Adenylyl Cyclases from Changes in Intracellular pH

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