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  • embryonic
  • Adrenal glucocorticoids Adrenal glucocorticoids regulate adaptation mechanisms to environmental challenges ( ) and can modify the electrical excitability of BK channels in human embryonic kidney cells. (epfl.ch)
  • Phosphorylation
  • NaV1.6 channels demonstrate resistance against protein phosphorylation regulation. (wikipedia.org)
  • Phosphorylation sites at amino acid residues Ser573 and Ser687 are found in other sodium channels but are not well conserved in NaV1.6. (wikipedia.org)
  • We asked whether the seizure-dependent downregulation of HCN channel gating was due to altered phosphorylation signaling mediated by the phosphatase calcineurin (CaN) or the kinase p38 mitogen-activated protein kinase (p38 MAPK). (jneurosci.org)
  • Pharmacological reversal of these phosphorylation changes restored HCN channel gating downregulation and neuronal hyperexcitability in epileptic tissue to control levels. (jneurosci.org)
  • Together, these results suggest that alteration of two different phosphorylation pathways in epilepsy contributes to the downregulation of HCN channel gating, which consequently produces neuronal hyperexcitability and thus may be a target for novel antiepileptic therapies. (jneurosci.org)
  • There is evidence of changes in BK channel activity by phosphorylation and/or interaction by G proteins, by mechanical stretch, and by various endothelium-derived vasoactive substances . (epfl.ch)
  • The protein has multiple predicted phosphorylation sites that can modulate channel function by phosphorylation . (epfl.ch)
  • Moreover, each type of neuronal BK channels are differentially sensitive to PKA-dependent phosphorylation. (epfl.ch)
  • current
  • Thus, the open-channel blocking protein responsible for resurgent current acts as a natural antagonist of lidocaine. (jneurosci.org)
  • Several clinically used compounds, such as lidocaine, also bind and block current through Na channels. (jneurosci.org)
  • When Na channels are placed in the axon, the soma acts as a current sink for the Na current. (plos.org)
  • Second, current-voltage relationships measured at the soma in vitro show an effective slope factor of about 1 mV, instead of the expected 6 mV . (plos.org)
  • inhibition
  • Pharmacological inhibition of CaN or activation of p38 MAPK partially reversed the in vitro seizure-induced hyperpolarized shift in HCN channel gating, and the shift was fully reversed by the combination of CaN inhibition and p38 MAPK activation. (jneurosci.org)
  • synaptic
  • N- and P/Q-type voltage-gated calcium channels are the primary subtypes found to support synaptic transmission. (wikipedia.org)
  • We examined the neuromodulatory effects of noradrenergic and GABA B receptor activation on synaptic inputs to the premotor robust nucleus of the arcopallium (RA) in zebra finches using whole cell voltage-clamp recording in vitro. (physiology.org)
  • inputs
  • Given the location of Nav1.6, the channel contributes to the firing threshold of a given neuron, as the electrical impulses from various inputs are summed at the axon hillock in order to reach firing threshold before propagating down the axon. (wikipedia.org)
  • Stuart and Spruston, 2015 ) and the axon that eventually converts these processed inputs into variable patterns of action potential (AP), with fast and robust transmission to distant postsynaptic targets. (frontiersin.org)
  • vivo
  • We then found that an in vitro model of seizures (1 h in 0 Mg 2+ and 50 μ m bicuculline at 35-37°C) reproduced the HCN channel gating change seen in vivo . (jneurosci.org)
  • We then demonstrated enhanced CaN activity as well as reduced p38 MAPK activity in vivo in the CA1 hippocampal area of chronically epileptic animals. (jneurosci.org)
  • We then found that an in vitro model of seizures replicated the downregulation of HCN channel gating observed in vivo after pilocarpine-induced SE. (jneurosci.org)
  • generate
  • Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit. (frontiersin.org)
  • abruptly
  • I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage. (plos.org)
  • signals
  • The voltage and metal sensors all control the opening of the same ionic pore in response to various physiological signals . (epfl.ch)
  • mammalian
  • Mammalian BK channels are characterized by their high sensitivity to blockade by iberiotoxin (IbTx) and charybdotoxin. (epfl.ch)
  • calcium
  • The IQ motif folds into a helix when interacting with CaM and CaM will inactivate NaV1.6 depending on the concentration of calcium. (wikipedia.org)
  • activation
  • Thus, we hypothesized that seizure-dependent downregulation of HCN channel gating might be due to CaN activation or loss of p38 MAPK activity. (jneurosci.org)
  • It was indeed shown that the cut-off frequency of signal transmission in the latter type of models is inversely related to the activation slope factor of Na channels. (plos.org)
  • cyclic
  • The onset of spontaneous seizures in the pilocarpine model of epilepsy causes a hyperpolarized shift in the voltage-dependent activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current ( I h ) in CA1 hippocampal pyramidal neuron dendrites, contributing to neuronal hyperexcitability and possibly to epileptogenesis. (jneurosci.org)
  • These can either be voltage-dependent channels taking part to regulation of neuronal electroresponsiveness, or be ionic cyclic nucleotide-gated channels (CNGCs) specifically involved in neuromodulatory responses. (frontiersin.org)
  • synaptic
  • It was concluded that L-type channels provide a means for differential control of spontaneous and impulse-evoked GABA release and that this differential control is prominent during short-term synaptic plasticity. (physiology.org)
  • We examined the neuromodulatory effects of noradrenergic and GABA B receptor activation on synaptic inputs to the premotor robust nucleus of the arcopallium (RA) in zebra finches using whole cell voltage-clamp recording in vitro. (physiology.org)
  • Several studies show an uneven distribution of ion channels and their differential regulation within dendrites and axons, which is a prerequisite for an appropriate integration of synaptic inputs and the generation of adequate action potential (AP) firing patterns. (frontiersin.org)
  • N- and P/Q-type voltage-gated calcium channels are the primary subtypes found to support synaptic transmission. (wikipedia.org)
  • inhibition
  • Pharmacological inhibition of CaN or activation of p38 MAPK partially reversed the in vitro seizure-induced hyperpolarized shift in HCN channel gating, and the shift was fully reversed by the combination of CaN inhibition and p38 MAPK activation. (jneurosci.org)
  • spike
  • A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. (plos.org)
  • Sodium channel availability decreased abruptly during the spike, as expected, but never reached zero. (physiology.org)
  • These features of sodium channel gating, especially the availability remaining after the spike, reduce the refractory period and facilitate rapid repetitive firing. (physiology.org)
  • With strong stimulation and repetitive fast firing, spike shape can change substantially and changes in spike shape could well affect sodium channel behavior. (physiology.org)
  • However, increased density of voltage-gated sodium channels may reduce the amplitude of a signal needed to initiate a spike. (wikipedia.org)
  • inputs
  • Stuart and Spruston, 2015 ) and the axon that eventually converts these processed inputs into variable patterns of action potential (AP), with fast and robust transmission to distant postsynaptic targets. (frontiersin.org)
  • Given the location of Nav1.6, the channel contributes to the firing threshold of a given neuron, as the electrical impulses from various inputs are summed at the axon hillock in order to reach firing threshold before propagating down the axon. (wikipedia.org)
  • current
  • When Na channels are placed in the axon, the soma acts as a current sink for the Na current. (plos.org)
  • Second, current-voltage relationships measured at the soma in vitro show an effective slope factor of about 1 mV, instead of the expected 6 mV . (plos.org)
  • Several clinically used compounds, such as lidocaine, also bind and block current through Na channels. (jneurosci.org)
  • vivo
  • We then found that an in vitro model of seizures (1 h in 0 Mg 2+ and 50 μ m bicuculline at 35-37°C) reproduced the HCN channel gating change seen in vivo . (jneurosci.org)
  • We then demonstrated enhanced CaN activity as well as reduced p38 MAPK activity in vivo in the CA1 hippocampal area of chronically epileptic animals. (jneurosci.org)
  • We then found that an in vitro model of seizures replicated the downregulation of HCN channel gating observed in vivo after pilocarpine-induced SE. (jneurosci.org)
  • generate
  • Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit. (frontiersin.org)
  • abruptly
  • I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage. (plos.org)
  • signals
  • The voltage and metal sensors all control the opening of the same ionic pore in response to various physiological signals . (epfl.ch)
  • Thus
  • Thus, we hypothesized that seizure-dependent downregulation of HCN channel gating might be due to CaN activation or loss of p38 MAPK activity. (jneurosci.org)
  • crucial
  • In contrast, L-type (Ca V 1) channels, which in similarity with P/Q- and N-types belong to the high-voltage-gated group, do not seem crucial for triggering transmitter release in fast conventional synapses. (physiology.org)
  • activation
  • It was indeed shown that the cut-off frequency of signal transmission in the latter type of models is inversely related to the activation slope factor of Na channels. (plos.org)
  • calcium
  • The IQ motif folds into a helix when interacting with CaM and CaM will inactivate NaV1.6 depending on the concentration of calcium. (wikipedia.org)
  • high
  • Mammalian BK channels are characterized by their high sensitivity to blockade by iberiotoxin (IbTx) and charybdotoxin. (epfl.ch)
  • GABA
  • Abbiamo generato una serie di mutanti C-terminale di GABA(B(1)) e GABA(B(2)) e li ha provati per interazione fisica, superficie traffico, giunto a adenil ciclasi e G-proteina-gated interiormente che rettifica canali del potassio in cellule di rene embrionale umano (HEK) 293, nonché sui canali calcio endogeno nel simpatici neuroni del ganglio cervicale superiore (SCG). (jove.com)
  • type
  • Block of L-type channels did not affect the sIPSC and mIPSC properties (frequency, amplitude, decay time course) in the absence of external stimulation but unexpectedly potentiated the eIPSCs evoked at low stimulus frequency (0.1-2.0 Hz). (physiology.org)
  • Block of L-type channels still potentiated the eIPSC during PTP, but in contrast, reduced the sIPSC frequency during PTP. (physiology.org)
  • Functional coupling of the presynaptic L-type channels to K Ca channels explains the observed effects on eIPSCs. (physiology.org)
  • A role of presynaptic L-type Ca 2+ channels has also been suggested for a few other central synapses. (physiology.org)
  • This apparently different role of L-type channels in hippocampal and midbrain synapses compared with MPN synapses raises the question how the contribution of L-type channels depends on the stimulus conditions, i.e., the presynaptic impulse frequency. (physiology.org)
  • The same type of voltage-gated channels may differ in distribution between the soma and dendrite within the same neuron. (wikipedia.org)