Calcium stores regulate excitability in cultured rat hippocampal neurons

Extracellular calcium ions support synaptic activity but also reduce excitability of central neurons. In the present study, the effect of calcium on excitability was explored in cultured hippocampal neurons. CaCl2 injected by pressure in the vicinity of a neuron that is bathed only in MgCl2 as the main divalent cation caused a depolarizing shift in action potential threshold and a reduction in excitability. This effect was not seen if the intracellular milieu consisted of Cs+ instead of K-gluconate as the main cation or when it contained ruthenium red, which blocks release of calcium from stores. The suppression of excitability by calcium was mimicked by caffeine, and calcium store antagonists cyclopiazonic acid or thapsigargin blocked this action. Neurons taken from synaptopodin-knockout mice show significantly reduced efficacy of calcium modulation of action potential threshold. Likewise, in Orai1 knockdown cells, calcium is less effective in modulating excitability of neurons. Activation of small-conductance K (SK) channels increased action potential threshold akin to that produced by calcium ions, whereas blockade of SK channels but not big K channels reduced the threshold for action potential discharge. These results indicate that calcium released from stores may suppress excitability of central neurons. NEW & NOTEWORTHY Extracellular calcium reduces excitability of cultured hippocampal neurons. This effect is mediated by calcium-gated potassium currents, possibly small-conductance K channels. Release of calcium from internal stores mimics the effect of extracellular calcium. It is proposed that calcium stores modulate excitability of central neurons.

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Altered Chloride Homeostasis Decreases the Action Potential Threshold and Increases Hyperexcitability in Hippocampal Neurons

eNeuro ◽

10.1523/eneuro.0172-17.2017 ◽

2017 ◽

Vol 4 (6) ◽

pp. ENEURO.0172-17.2017 ◽

Cited By ~ 10

Author(s):

Andreas T. Sørensen ◽

Marco Ledri ◽

Miriam Melis ◽

Litsa Nikitidou Ledri ◽

My Andersson ◽

...

Keyword(s):

Action Potential ◽

Hippocampal Neurons ◽

Chloride Homeostasis ◽

Action Potential Threshold ◽

Potential Threshold

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Small-conductance Ca2+-activated K+ channels modulate action potential-induced Ca2+ transients in hippocampal neurons

Journal of Neurophysiology ◽

10.1152/jn.00346.2012 ◽

2013 ◽

Vol 109 (6) ◽

pp. 1514-1524 ◽

Cited By ~ 9

Author(s):

Raffaella Tonini ◽

Teresa Ferraro ◽

Marisol Sampedro-Castañeda ◽

Anna Cavaccini ◽

Martin Stocker ◽

...

Keyword(s):

Action Potential ◽

Action Potentials ◽

Hippocampal Neurons ◽

Pyramidal Neurons ◽

Apical Dendrite ◽

Channel Blockers ◽

Sk Channels ◽

Hippocampal Pyramidal Neurons ◽

Voltage Gated ◽

Small Conductance

In hippocampal pyramidal neurons, voltage-gated Ca2+ channels open in response to action potentials. This results in elevations in the intracellular concentration of Ca2+ that are maximal in the proximal apical dendrites and decrease rapidly with distance from the soma. The control of these action potential-evoked Ca2+ elevations is critical for the regulation of hippocampal neuronal activity. As part of Ca2+ signaling microdomains, small-conductance Ca2+-activated K+ (SK) channels have been shown to modulate the amplitude and duration of intracellular Ca2+ signals by feedback regulation of synaptically activated Ca2+ sources in small distal dendrites and dendritic spines, thus affecting synaptic plasticity in the hippocampus. In this study, we investigated the effect of the activation of SK channels on Ca2+ transients specifically induced by action potentials in the proximal processes of hippocampal pyramidal neurons. Our results, obtained by using selective SK channel blockers and enhancers, show that SK channels act in a feedback loop, in which their activation by Ca2+ entering mainly through L-type voltage-gated Ca2+ channels leads to a reduction in the subsequent dendritic influx of Ca2+. This underscores a new role of SK channels in the proximal apical dendrite of hippocampal pyramidal neurons.

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Calcium-induced calcium release activates spontaneous miniature outward currents in newt medullary reticular formation neurons

Journal of Neurophysiology ◽

10.1152/jn.00616.2017 ◽

2018 ◽

Vol 120 (6) ◽

pp. 3140-3154 ◽

Cited By ~ 2

Author(s):

Daniel B. Yaeger ◽

Emma J. Coddington

Keyword(s):

Action Potential ◽

Reticular Formation ◽

Calcium Release ◽

Motor Behavior ◽

Brain Slices ◽

Medullary Reticular Formation ◽

Outward Currents ◽

Decay Times ◽

Action Potential Threshold ◽

Potential Threshold

Neurons in the medullary reticular formation are involved in the control of postural and locomotor behaviors in all vertebrates. Reticulospinal neurons in this brain region provide one of the major descending projections to the spinal cord. Although neurons in the newt medullary reticular formation have been extensively studied using in vivo extracellular recordings, little is known of their intrinsic biophysical properties or of the underlying circuitry of this region. Using whole cell patch-clamp recordings in brain slices containing the rostromedial reticular formation from adult male newts, we observed spontaneous miniature outward currents (SMOCs) in ~2/3 of neurons. Although SMOCs superficially resembled inhibitory postsynaptic currents (IPSCs), they had slower risetimes and decay times than spontaneous IPSCs. SMOCs required intracellular Ca2+ release from ryanodine receptors and were also dependent on the influx of extracellular Ca2+. SMOCs were unaffected by apamin but were partially blocked by iberiotoxin and charybdotoxin, indicating that SMOCs were mediated by big-conductance Ca2+-activated K+ channels. Application of the sarco/endoplasmic Ca2+ ATPase inhibitor cyclopiazonic acid blocked the generation of SMOCs and also increased neural excitability. Neurons with SMOCs had significantly broader action potentials, slower membrane time constants, and higher input resistance than neurons without SMOCs. Thus, SMOCs may serve as a mechanism to regulate action potential threshold in a majority of neurons within the newt medullary reticular formation. NEW & NOTEWORTHY The medullary reticular formation exerts a powerful influence on sensorimotor integration and subsequent motor behavior, yet little is known about the neurons involved. In this study, we identify a transient potassium current that regulates action potential threshold in a majority of medullary reticular neurons.

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Calcium Sensors STIM1 and STIM2 Regulate Different Calcium Functions in Cultured Hippocampal Neurons

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2020.573714 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liliya Kushnireva ◽

Eduard Korkotian ◽

Menahem Segal

Keyword(s):

Dendritic Spines ◽

Hippocampal Neurons ◽

Calcium Entry ◽

Calcium Stores ◽

Plastic Properties ◽

Calcium Sensors ◽

Central Neurons ◽

Transient Rise ◽

Store Operated Calcium Entry ◽

Adult Neuron

There are growing indications for the involvement of calcium stores in the plastic properties of neurons and particularly in dendritic spines of central neurons. The store-operated calcium entry (SOCE) channels are assumed to be activated by the calcium sensor stromal interaction molecule (STIM)which leads to activation of its associated Orai channel. There are two STIM species, and the differential role of the two in SOCE is not entirely clear. In the present study, we were able to distinguish between transfected STIM1, which is more mobile primarily in young neurons, and STIM2 which is less mobile and more prominent in older neurons in culture. STIM1 mobility is associated with spontaneous calcium sparks, local transient rise in cytosolic [Ca2+]i, and in the formation and elongation of dendritic filopodia/spines. In contrast, STIM2 is associated with older neurons, where it is mobile and moves into dendritic spines primarily when cytosolic [Ca2+]i levels are reduced, apparently to activate resident Orai channels. These results highlight a role for STIM1 in the regulation of [Ca2+]i fluctuations associated with the formation of dendritic spines or filopodia in the developing neuron, whereas STIM2 is associated with the maintenance of calcium entry into stores in the adult neuron.

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