Persistent Sodium Current in Mammalian Central Neurons

Crill, W. E.

doi:10.1146/annurev.ph.58.030196.002025

Cited by 577 publications

(351 citation statements)

References 45 publications

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“…The amplitude of the singleaxon excitatory postsynaptic potentials is variable, in a range from 0.1 to 9 mV with a total mean Ϸ1 mV (38)(39)(40)(41)(42). In addition, our recent data suggest that a persistent sodium current (43)(44)(45) takes part in the maintenance of the depolarizing states of the membrane potential that are found during waking, REM and depolarizing phases of SWS (46). This indicates that very strong synaptic and intrinsic depolarizing pressure is experienced by neocortical neurons, which would result in extremely high firing rates.…”

Section: Discussionmentioning

confidence: 91%

Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: An intracellular study

Timofeev¹

2001

Proceedings of the National Academy of Sciences

163

169

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Earlier extracellular recordings during natural sleep have shown that, during slow-wave sleep (SWS), neocortical neurons display long-lasting periods of silence, whereas they are tonically active and discharge at higher rates during waking and sleep with rapid eye movements (REMs). We analyzed the nature of long-lasting periods of neuronal silence in SWS and the changes in firing rates related to ocular movements during REM sleep and waking using intracellular recordings from electrophysiologically identified neocortical neurons in nonanesthetized and nonparalyzed cats. We found that the silent periods during SWS are associated with neuronal hyperpolarizations, which are due to a mixture of K ؉ currents and disfacilitation processes. Conventional fast-spiking neurons (presumably local inhibitory interneurons) increased their firing rates during REMs and eye movements in waking. During REMs, the firing rates of regular-spiking neurons from associative areas decreased and intracellular traces revealed numerous, shortlasting, low-amplitude inhibitory postsynaptic potentials (IPSPs), that were reversed after intracellular chloride infusion. In awake cats, regular-spiking neurons could either increase or decrease their firing rates during eye movements. The short-lasting IPSPs associated with eye movements were still present in waking; they preceded the spikes and affected their timing. We propose that there are two different forms of firing rate control: disfacilitation induces long-lasting periods of silence that occur spontaneously during SWS, whereas active inhibition, consisting of low-amplitude, short-lasting IPSPs, is prevalent during REMs and precisely controls the timing of action potentials in waking.

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Section: Discussionmentioning

confidence: 91%

Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: An intracellular study

Timofeev¹

2001

Proceedings of the National Academy of Sciences

163

169

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“…BgNa v 7 has a significant overlap between the voltage dependence of activation and the voltage dependence of steady-state inactivation, with V 1 ⁄2 values of Ϫ36.7 and Ϫ37.2 mV for activation and inactivation, respectively. Consequently, this variant produces a large window current over a range of Ϫ45 mV to Ϫ25 mV, which could lead to membrane depolarization at subthreshold potentials, resulting in oscillatory activities, summation of synaptic input, or controlling firing frequency, and so on (32). Thus, even though insects carry only a single sodium channel gene, a combination of alternative splicing and RNA editing of the primary transcript can apparently produce a full complement of functionally diverse sodium channels.…”

Section: Discussionmentioning

confidence: 99%

RNA Editing Generates Tissue-specific Sodium Channels with Distinct Gating Properties

Song¹,

Liu²,

Tan

et al. 2004

Journal of Biological Chemistry

100

140

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“…QX-314 in the pipette decreased both their amplitude and incidence, consistent with the activation of K ϩ conductances during the prolonged hyperpolarizations. QX-314 affects a wide range of membrane conductances, including the blockade of fast and persistent Na ϩ currents (26), low-and high-voltage activated Ca 2ϩ currents (27), K ϩ currents (28,29), and hyperpolarization-activated currents (30). It is unlikely that depolarizing (Ca 2ϩ and Na ϩ ) currents are implicated in the genesis of the prolonged hyperpolarizations.…”

Section: Discussionmentioning

confidence: 99%

Prolonged hyperpolarizing potentials precede spindle oscillations in the thalamic reticular nucleus

Fuentealba

Timofeev

Steriade

2004

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

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The thalamic reticular (RE) nucleus is a key structure in the generation of spindles, a hallmark bioelectrical oscillation during early stages of sleep. Intracellular recordings of RE neurons in vivo revealed the presence of prolonged hyperpolarizing potentials preceding spindles in a subgroup (30%) of neurons. These hyperpolarizations (6 -10 mV) lasted for 200 -300 ms and were present just before the onset of spontaneously occurring spindle waves. Corticothalamic volleys also were effective in generating such hyperpolarizations followed by spindles in RE neurons. A drop of up to 40% in the apparent input resistance (Rin) was associated with these hyperpolarizing potentials, suggesting an active process rather than disfacilitation. Accordingly, the reversal potential was approximately ؊100 mV for both spontaneous and cortically elicited hyperpolarizations, consistent with the activation of slow K ؉ conductances. QX-314 in the recording pipettes decreased both the amplitude and incidence of prolonged hyperpolarizations, suggesting the participation of G protein-dependent K ؉ currents in the generation of hyperpolarizations. Simultaneous extracellular and intracellular recordings in the RE nucleus demonstrated that some RE neurons discharged during the hyperpolarizations and, thus, may be implicated in their generation. The prolonged hyperpolarizations preceding spindles may play a role in the transition from tonic to bursting firing of RE neurons within a range of membrane potential (؊60 to ؊65 mV) at which they set favorable conditions for the generation of low-threshold spike bursts that initiate spindle sequences. These data are further arguments for the generation of spindles within the thalamic RE nucleus.S pindles (7-15 Hz) are a hallmark oscillation during early sleep states. During the past two decades, a series of studies have demonstrated that spindles are generated within the thalamic reticular (RE) nucleus, which is uniquely composed of neurons using ␥-aminobutyric acid (GABA) as neurotransmitter. Spindles are transferred to the cerebral cortex through the interactions between RE and thalamocortical neurons. Thus, experimental evidence has shown that spindles are abolished in thalamocortical systems after lesions of RE neurons or transections separating them from thalamocortical neurons (1) but survive in the RE nucleus deafferented from the dorsal thalamus and cerebral cortex (2). Computational studies agreed with the initiation of spindle rhythmicity in the isolated RE nucleus (3-5) and suggested that, at relatively hyperpolarized levels of membrane potential (V m ), as is the case during slow-wave sleep, the inhibitory postsynaptic potentials (IPSPs) between RE neurons can be reversed, and GABA A -mediated depolarizing potentials can generate persistent spatio-temporal patterns in the RE nucleus (6). The transfer of spindles from the RE nucleus, which is devoid of cortical projections, to the cerebral cortex is caused by RE cells' interactions with thalamocortical neurons (7-9).The mechanisms under...

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Persistent Sodium Current in Mammalian Central Neurons

Cited by 577 publications

References 45 publications

Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: An intracellular study

Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: An intracellular study

RNA Editing Generates Tissue-specific Sodium Channels with Distinct Gating Properties

Prolonged hyperpolarizing potentials precede spindle oscillations in the thalamic reticular nucleus

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