Effect of Divalent Cations on AMPA-Evoked Extracellular Alkaline Shifts in Rat Hippocampal Slices

1999 ◽  
Vol 82 (4) ◽  
pp. 1902-1908 ◽  
Author(s):  
S. E. Smith ◽  
M. Chesler
Keyword(s):  
Carbonic Anhydrase ◽  
Calcium Channels ◽  
Divalent Cations ◽  
Hippocampal Slices ◽  
Strong Base ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Alkaline Shift ◽  
Ca1 Area ◽  
Activity Dependent

The generation of activity-evoked extracellular alkaline shifts has been linked to the presence of external Ca2+ or Ba2+. We further investigated this dependence using pH- and Ca2+-selective microelectrodes in the CA1 area of juvenile, rat hippocampal slices. In HEPES-buffered media, alkaline transients evoked by pressure ejection of RS-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) averaged ∼0.07 unit pH and were calculated to arise from the equivalent net addition of ∼1 mM strong base to the interstitial space. These alkaline responses were correlated with a mean decrease in [Ca2+]o of ∼300 μM. The alkalinizations were abolished reversibly in zero-Ca2+ media, becoming indiscernible at a [Ca2+]o of 117 ± 29 μM. Addition of as little as 30–50 μM Ba2+ caused the reappearance of an alkaline response. In approximately one-fourth of slices, a persistent alkaline shift of ∼0.03 unit pH was observed in zero-Ca2+ saline containing EGTA. In HEPES media, addition of 300 μM Cd2+, 100 μM Ni2+, or 100 μM nimodipine inhibited the alkaline shifts by roughly one-half, one-third, and one-third, respectively, whereas Cd+ and Ni2+ in combination fully blocked the response. In bicarbonate media, by contrast, Cd+ and Ni2+blocked only two-thirds of the response. In the presence of bicarbonate, Ni2+ caused an unexpected enhancement of the alkalinization by ∼150%. However, when the extracellular carbonic anhydrase was blocked by benzolamide, addition of Ni2+reduced the alkaline shift. These results suggested that Ni2+ partially inhibited the interstitial carbonic anhydrase and thereby increased the alkaline responses. These data indicate that an activity-dependent alkaline shift is largely dependent on the entry of Ca2+ or Ba2+ via voltage-gated calcium channels. However, sizable alkaline transients still can be generated with little or no external presence of these ions. Implications for the mechanism of the activity-dependent alkaline shift are discussed.

Role of voltage-gated calcium channels in the generation of activity-induced extracellular pH transients in the rat hippocampal slice

1996 ◽  
Vol 75 (6) ◽  
pp. 2354-2360 ◽  
Author(s):  
P. Paalasmaa ◽  
K. Kaila
Keyword(s):  
Calcium Channels ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Extracellular Ph ◽  
Stratum Radiatum ◽  
Gamma Aminobutyric Acid ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Alkaline Shift

1. The role of voltage-gated calcium channels in the generation of activity-induced alkaline shifts in extracellular pH (pHo) was studied in rat hippocampal slices (area CAI) by means of Ca(2+)-and H(+)-selective microlectrodes inserted into the stratum pyramidale and/or stratum radiatum. 2. After complete pharmacological blockade of ionotropic glutamate receptors and gamma-aminobutyric acid-A (GABAA) receptors, trains (5-10 Hz, 5-10s) of antidromic spikes in pyramidal neurons were associated with a fast alkaline transient of up to 0.17 pH units and a fall in the extracellular Ca2+ concentration ([Ca2+]o). The alkaline shift was strongly enhanced upon inhibition of extracellular carbonic anhydrase. 3. Application of 100 microM Ni2+ plus 100 microM Cd2+ inhibited both the fall in [Ca2+]o and the alkaline transient triggered by antidromic spikes. The alkaline shift was abolished in the absence of extracellular Ca2+. 4. In the absence of postsynaptic receptor antagonists, alkaline transients linked to a given level of synaptic excitation in s. radiatum were strongly suppressed after blockade of somatic (and, consequently, of dendritic “backpropagating”) spikes by microdrop application of tetrodotoxin to the cell-body layer. 5. We have previously shown that activity-induced alkaline transients in the CAI region are due to an influx of Ca2+ into neurons, which triggers an influx of H+ ions probably caused by activation of a plasmalemmal Ca2+/H+ ATPase. The present results indicate that much (in s. pyramidale perhaps all) of the pH-changing influx of Ca2+ is mediated by voltage-gated Ca2+ channels.

scholarly journals Ca2+ entry through NaV channels generates submillisecond axonal Ca2+ signaling

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Naomi AK Hanemaaijer ◽  
Marko A Popovic ◽  
Xante Wilders ◽  
Sara Grasman ◽  
Oriol Pavón Arocas ◽  
...  
Keyword(s):  
Calcium Channels ◽  
High Speed ◽  
Initial Segment ◽  
Hek 293 ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
293 Cells ◽  
Axonal Initial Segment ◽  
Nav Channels ◽  
Activity Dependent

Calcium ions (Ca2+) are essential for many cellular signaling mechanisms and enter the cytosol mostly through voltage-gated calcium channels. Here, using high-speed Ca2+ imaging up to 20 kHz in the rat layer five pyramidal neuron axon we found that activity-dependent intracellular calcium concentration ([Ca2+]i) in the axonal initial segment was only partially dependent on voltage-gated calcium channels. Instead, [Ca2+]i changes were sensitive to the specific voltage-gated sodium (NaV) channel blocker tetrodotoxin. Consistent with the conjecture that Ca2+ enters through the NaV channel pore, the optically resolved ICa in the axon initial segment overlapped with the activation kinetics of NaV channels and heterologous expression of NaV1.2 in HEK-293 cells revealed a tetrodotoxin-sensitive [Ca2+]i rise. Finally, computational simulations predicted that axonal [Ca2+]i transients reflect a 0.4% Ca2+ conductivity of NaV channels. The findings indicate that Ca2+ permeation through NaV channels provides a submillisecond rapid entry route in NaV-enriched domains of mammalian axons.

scholarly journals 1,25-Dihydroxyvitamin D modulates L-type voltage-gated calcium channels in a subset of neurons in the developing mouse prefrontal cortex

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Helen Gooch ◽  
Xiaoying Cui ◽  
Victor Anggono ◽  
Maciej Trzaskowski ◽  
Men Chee Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Prefrontal Cortex ◽  
Calcium Channels ◽  
Brain Maturation ◽  
Genome Wide Association Studies ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Enhanced Activity ◽  
Activity Dependent

Abstract Schizophrenia has been associated with a range of genetic and environmental risk factors. Here we explored a link between two risk factors that converge on a shared neurobiological pathway. Recent genome-wide association studies (GWAS) have identified risk variants in genes that code for L-type voltage-gated calcium channels (L-VGCCs), while epidemiological studies have found an increased risk of schizophrenia in those with neonatal vitamin D deficiency. The active form of vitamin D (1,25(OH)2D) is a secosteroid that rapidly modulates L-VGCCs via non-genomic mechanisms in a range of peripheral tissues, though its non-genomic effects within the brain remain largely unexplored. Here we used calcium imaging, electrophysiology and molecular biology to determine whether 1,25(OH)2D non-genomically modulated L-VGCCs in the developing prefrontal cortex, a region widely implicated in schizophrenia pathophysiology. Wide-field Ca2+ imaging revealed that physiological concentrations of 1,25(OH)2D rapidly enhanced activity-dependent somatic Ca2+ levels in a small subset of neurons in the developing PFC, termed vitamin D-responsive neurons (VDRNs). Somatic nucleated patch recordings revealed a rapid, 1,25(OH)2D-evoked increase in high-voltage-activated (HVA) Ca2+ currents. Enhanced activity-dependent Ca2+ levels were mediated by L-VGCC but not associated with any changes to Cacna1c (L-VGCC pore-forming subunit) mRNA expression. Since L-VGCC activity is critical to healthy neurodevelopment, these data suggest that suboptimal concentrations of 1,25(OH)2D could alter brain maturation through modulation of L-VGCC signalling and as such may provide a parsimonious link between epidemiologic and genetic risk factors for schizophrenia.

AMPA Induces NO-Dependent cGMP Signals in Hippocampal and Cortical Neurons via L-Type Voltage-Gated Calcium Channels

2019 ◽  
Vol 30 (4) ◽  
pp. 2128-2143 ◽  
Author(s):  
Jan Giesen ◽  
Ernst-Martin Füchtbauer ◽  
Annette Füchtbauer ◽  
Klaus Funke ◽  
Doris Koesling ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Cortical Neurons ◽  
Calcium Influx ◽  
Hippocampal Slices ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Acute Hippocampal Slices ◽  
The Impact

Abstract The nitric oxide (NO)/cGMP signaling cascade has an established role in synaptic plasticity. However, with conventional methods, the underlying cGMP signals were barely detectable. Here, we set out to confirm the well-known NMDA-induced cGMP increases, to test the impact of AMPA on those signals, and to identify the relevant phosphodiesterases (PDEs) using a more sensitive fluorescence resonance energy transfer (FRET)-based method. Therefore, a “knock-in” mouse was generated that expresses a FRET-based cGMP indicator (cGi-500) allowing detection of cGMP concentrations between 100 nM and 3 μM. Measurements were performed in cultured hippocampal and cortical neurons as well as acute hippocampal slices. In hippocampal and cortical neurons, NMDA elicited cGMP signals half as high as the ones elicited by exogenous NO. Interestingly, AMPA increased cGMP independently of NMDA receptors and dependent on NO synthase (NOS) activation. NMDA- and AMPA-induced cGMP signals were not additive indicating that both pathways converge on the level of NOS. Accordingly, the same PDEs, PDE1 and PDE2, were responsible for degradation of NMDA- as well as AMPA-induced cGMP signals. Mechanistically, AMPAR induced calcium influx through L-type voltage-gated calcium channels leading to NOS and finally NO-sensitive guanylyl cyclase activation. Our results demonstrate that in addition to NMDA also AMPA triggers endogenous NO formation and hence cGMP production.

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