Remacemide HC1 and its metabolite, FPL 12495AA, limit action potential firing frequency and block NMDA responses of mouse spinal cord neurons in cell culture

The prevailing view of epileptic seizures is that they are caused by increased hypersynchronous activity in the cortical network. However, this view is based mostly on electroencephalography (EEG) recordings that do not directly monitor neuronal synchronization of action potential firing. In this study, we used multielectrode single-unit recordings from the hippocampus to investigate firing of individual CA1 neurons and directly monitor synchronization of action potential firing between neurons during the different ictal phases of chemoconvulsant-induced epileptic seizures in vivo. During the early phase of seizures manifesting as low-amplitude rhythmic β-electrocorticography (ECoG) activity, the firing frequency of most neurons markedly increased. To our surprise, the average overall neuronal synchronization as measured by the cross-correlation function was reduced compared with control conditions with ∼60% of neuronal pairs showing no significant correlated firing. However, correlated firing was not uniform and a minority of neuronal pairs showed a high degree of correlated firing. Moreover, during the early phase of seizures, correlated firing between 9.8 ± 5.1% of all stably recorded pairs increased compared with control conditions. As seizures progressed and high-frequency ECoG polyspikes developed, the firing frequency of neurons further increased and enhanced correlated firing was observed between virtually all neuronal pairs. These findings indicated that epileptic seizures represented a hyperactive state with widespread increase in action potential firing. Hypersynchrony also characterized seizures. However, it initially developed in a small subset of neurons and gradually spread to involve the entire cortical network only in the later more intense ictal phases.

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Calcium-dependent action potentials in mouse spinal cord neurons in cell culture

Brain Research ◽

10.1016/0006-8993(81)91234-8 ◽

1981 ◽

Vol 220 (2) ◽

pp. 408-415 ◽

Cited By ~ 17

Author(s):

Eric J. Heyer ◽

Robert L. Macdonald ◽

Gregory K. Bergey ◽

Phillip G. Nelson

Keyword(s):

Spinal Cord ◽

Cell Culture ◽

Action Potentials ◽

Spinal Cord Neurons ◽

Mouse Spinal Cord ◽

Calcium Dependent

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Zonal variations in K+ currents in vestibular crista calyx terminals

Journal of Neurophysiology ◽

10.1152/jn.00399.2014 ◽

2015 ◽

Vol 113 (1) ◽

pp. 264-276 ◽

Cited By ~ 13

Author(s):

Frances L. Meredith ◽

Katherine J. Rennie

Keyword(s):

Action Potential ◽

Ampa Receptors ◽

Channel Blocker ◽

Outward Current ◽

Firing Frequency ◽

Action Potential Firing ◽

Regional Variations ◽

Electrophysiological Properties ◽

Kcnq Channels ◽

Potential Firing

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones. Firing was abolished when extracellular choline replaced Na+ but persisted when hair cell mechanotransduction channels or calyx AMPA receptors were blocked. This suggests that ion channels intrinsic to the calyx can generate spontaneous firing. In response to depolarizing voltage steps, outward K+ currents were observed at potentials above −60 mV. K+ currents in PZ calyces showed significantly more inactivation than currents in CZ calyces. Underlying K+ channel populations contributing to these differences were investigated. The KCNQ channel blocker XE991 dihydrochloride blocked a slowly activating, sustained outward current in both PZ and CZ calyces, indicating the presence of KCNQ channels. Mean reduction was greatest in PZ calyces. XE991 also reduced action potential firing frequency in CZ and PZ calyces and broadened mean action potential width. The K+ channel blocker 4-aminopyridine (10–50 μM) blocked rapidly activating, moderately inactivating currents that were more prevalent in PZ calyces. α-Dendrotoxin, a selective blocker of KV1 channels, reduced outward currents in CZ calyces but not in PZ calyces. Regional variations in K+ conductances may contribute to different firing responses in calyx afferents.

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Propofol and Sevoflurane Depress Spinal Neurons In Vitro via Different Molecular Targets

Anesthesiology ◽

10.1097/00000542-200411000-00017 ◽

2004 ◽

Vol 101 (5) ◽

pp. 1167-1176 ◽

Cited By ~ 51

Author(s):

Christian Grasshoff ◽

Bernd Antkowiak

Keyword(s):

Spinal Cord ◽

Action Potential ◽

Gabaa Receptors ◽

Molecular Targets ◽

Glycine Receptors ◽

Spinal Neurons ◽

Action Potential Firing ◽

Spontaneous Action Potential ◽

Potential Firing ◽

Spontaneous Action

Background The capacity of general anesthetics to produce immobility is primarily spinally mediated. Recently, compelling evidence has been provided that the spinal actions of propofol involve gamma-aminobutyric acid type A (GABAA) receptors, whereas the contribution of glycine receptors remains uncertain. The relevant molecular targets of the commonly used volatile anesthetic sevoflurane in the spinal cord are largely unknown, but indirect evidence suggests a mechanism of action distinct from propofol. Methods The effects of sevoflurane and propofol on spontaneous action potential firing were investigated by extracellular voltage recordings from ventral horn interneurons in cultured spinal cord tissue slices obtained from embryonic rats (embryonic days 14-15). Results Propofol and sevoflurane reduced spontaneous action potential firing of neurons. Concentrations causing half-maximal effects (0.11 microm propofol, 0.11 mm sevoflurane) were lower than the median effective concentration immobility (1-1.5 microm propofol, 0.35 mm sevoflurane). At higher concentrations, complete inhibition of action potential activity was observed with sevoflurane but not with propofol. Effects of sevoflurane were mediated predominantly by glycine receptors (45%) and GABAA receptors (38%), whereas propofol acted almost exclusively via GABAA receptors (96%). Conclusions The authors' results suggest that glycine and GABAA receptors are the most important molecular targets mediating depressant effects of sevoflurane in the spinal cord. They provide evidence that sevoflurane causes immobility by a mechanism distinct from the actions of the intravenous anesthetic propofol. The finding that propofol acts exclusively via GABAA receptors can explain its limited capacity to depress spinal neurons in the authors' study.

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Substance P: ionic basis for depolarizing responses of mouse spinal cord neurons in cell culture

Journal of Neuroscience ◽

10.1523/jneurosci.02-08-01119.1982 ◽

1982 ◽

Vol 2 (8) ◽

pp. 1119-1128 ◽

Cited By ~ 73

Author(s):

LM Nowak ◽

RL Macdonald

Keyword(s):

Spinal Cord ◽

Cell Culture ◽

Substance P ◽

Spinal Cord Neurons ◽

Mouse Spinal Cord ◽

Ionic Basis

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Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons

eLife ◽

10.7554/elife.10013 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 22

Author(s):

Pedro L Martinez-Espinosa ◽

Jianping Wu ◽

Chengtao Yang ◽

Vivian Gonzalez-Perez ◽

Huifang Zhou ◽

...

Keyword(s):

Action Potential ◽

Small Diameter ◽

Firing Frequency ◽

Drg Neurons ◽

Action Potential Firing ◽

Discernible Effect ◽

Potential Firing ◽

Mammalian Genes ◽

Isolectin B4 ◽

Tools And Methods

Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.

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