Extracellular Potassium and Seizures: Excitation, Inhibition and the Role of Ih

2016 ◽  
Vol 26 (08) ◽  
pp. 1650044 ◽  
Author(s):  
Lihua Wang ◽  
Suzie Dufour ◽  
Taufik A. Valiante ◽  
Peter L. Carlen
Keyword(s):  
Neuronal Excitability ◽  
Seizure Activity ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Extracellular Potassium ◽  
Hcn Channels ◽  
Extracellular Potassium Concentration ◽  
Prolonged Seizure

Seizure activity leads to increases in extracellular potassium concentration ([K[Formula: see text]]o), which can result in changes in neuronal passive and active membrane properties as well as in population activities. In this study, we examined how extracellular potassium modulates seizure activities using an acute 4-AP induced seizure model in the neocortex, both in vivo and in vitro. Moderately elevated [K[Formula: see text]]o up to 9[Formula: see text]mM prolonged seizure durations and shortened interictal intervals as well as depolarized the neuronal resting membrane potential (RMP). However, when [K[Formula: see text]]o reached higher than 9[Formula: see text]mM, seizure like events (SLEs) were blocked and neurons went into a depolarization-blocked state. Spreading depression was never observed as the blockade of ictal events could be reversed within 1–2[Formula: see text]min after the raised [K[Formula: see text]]o was changed back to control levels. This concentration-dependent dual effect of [K[Formula: see text]]o was observed using in vivo and in vitro mouse brain preparations as well as in human neocortical tissue resected during epilepsy surgery. Blocking the Ih current, mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, modulated the elevated [K[Formula: see text]]o influence on SLEs by promoting the high [K[Formula: see text]]o inhibitory actions. These results demonstrate biphasic actions of raised [K[Formula: see text]]o on neuronal excitability and seizure activity.

scholarly journals Association of the Kv1 family of K+ channels and their functional blueprint in the properties of auditory neurons as revealed by genetic and functional analyses

2013 ◽  
Vol 110 (8) ◽  
pp. 1751-1764 ◽  
Author(s):  
Wenying Wang ◽  
Hyo Jeong Kim ◽  
Ping Lv ◽  
Bruce Tempel ◽  
Ebenezer N. Yamoah
Keyword(s):  
Membrane Potential ◽  
Developmental Plasticity ◽  
Spiral Ganglion ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Underlying Mechanisms ◽  
Null Mutant Mice ◽  
Ganglion Neurons

Developmental plasticity in spiral ganglion neurons (SGNs) ensues from profound alterations in the functional properties of the developing hair cell (HC). For example, prehearing HCs are spontaneously active. However, at the posthearing stage, HC membrane properties transition to graded receptor potentials. The dendrotoxin (DTX)-sensitive Kv1 channel subunits (Kv1.1, 1.2, and 1.6) shape the firing properties and membrane potential of SGNs, and the expression of the channel undergoes developmental changes. Because of the stochastic nature of Kv subunit heteromultimerization, it has been difficult to determine physiologically relevant subunit-specific interactions and their functions in the underlying mechanisms of Kv1 channel plasticity in SGNs. Using Kcna2 null mutant mice, we demonstrate a surprising paradox in changes in the membrane properties of SGNs. The resting membrane potential of Kcna2−/− SGNs was significantly hyperpolarized compared with that of age-matched wild-type (WT) SGNs. Analyses of outward currents in the mutant SGNs suggest an apparent approximately twofold increase in outward K+ currents. We show that in vivo and in vitro heteromultimerization of Kv1.2 and Kv1.4 α-subunits underlies the striking and unexpected alterations in the properties of SGNs. The results suggest that heteromeric interactions of Kv1.2 and Kv1.4 dominate the defining features of Kv1 channels in SGNs.

scholarly journals Lamotrigine Attenuates Neuronal Excitability, Depresses GABA Synaptic Inhibition, and Modulates Theta Rhythms in Rat Hippocampus

2021 ◽  
Author(s):  
Paulina Kazmierska-Grebowska ◽  
Marcin Siwiec ◽  
Joanna Ewa Sowa ◽  
Caban Bartosz ◽  
Tomasz Kowalczyk ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Medial Septum ◽  
Movement Planning ◽  
Theta Oscillations ◽  
Hcn Channels ◽  
Anaesthetized Rats ◽  
Hippocampal Theta

Theta oscillations generated in hippocampal (HPC) and cortical neuronal networks are involved in various aspects of brain function, including sensorimotor integration, movement planning, memory formation and attention. Disruptions of theta rhythms are present in individuals with various disorders, including epilepsy and Alzheimer’s disease. Theta rhythm generation involves a specific interplay between cellular (ionic) and network (synaptic) mechanisms. HCN channels are theta modulators, and several medications are known to enhance their activity. We investigated how different doses of lamotrigine (LTG), an HCN channel activator, and antiepileptic and neuroprotective agent, would affect hippocampal theta rhythms in acute HPC slices (in vitro) and anaesthetized rats (in vivo). Whole-cell patch clamp recordings revealed that LTG decreased GABAA-fast transmission in CA3 and CA1 cells, in vitro. In addition, LTG directly depressed CA3 and CA1 pyramidal neuron excitability. These effects were partially blocked by ZD 7288, a selective HCN blocker, and are consistent with decreased excitability associated with antiepileptic actions. Lamotrigine also depressed hippocampal theta oscillations in vitro, also consistent with its neuronal depressant effects. In contrast, it exerted an opposite, enhancing effect, on theta recorded in vivo. The contradictory in vivo and in vitro results indicate that LTG increases ascending theta activating medial septum/entorhinal synaptic inputs that over-power the depressant effects seen in hippocampal neurons. These results provide new insights into LTG actions and indicate an opportunity to develop more precise therapeutics for the treatment of dementias, memory disorders and epilepsy.

Increasing Extracellular Potassium Results in Subthalamic Neuron Activity Resembling That Seen in a 6-Hydroxydopamine Lesion

2008 ◽  
Vol 99 (6) ◽  
pp. 2902-2915 ◽  
Author(s):  
Ulf Strauss ◽  
Fu-Wen Zhou ◽  
Jeannette Henning ◽  
Arne Battefeld ◽  
Andreas Wree ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Potassium Concentration ◽  
Neuron Activity ◽  
Extracellular Potassium ◽  
Action Potential Firing ◽  
Extracellular Potassium Concentration ◽  
Potential Firing ◽  
6 Hydroxydopamine

Abnormal neuronal activity in the subthalamic nucleus (STN) plays a crucial role in the pathophysiology of Parkinson's disease (PD). Although altered extracellular potassium concentration ([K+]o) and sensitivity to [K+]o modulates neuronal activity, little is known about the potassium balance in the healthy and diseased STN. In vivo measurements of [K+]o using ion-selective electrodes demonstrated a twofold increase in the decay time constant of lesion-induced [K+]o transients in the STN of adult Wistar rats with a unilateral 6-hydroxydopamine (6-OHDA) median forebrain bundle lesion, employed as a model of PD, compared with nonlesioned rats. Various [K+]o concentrations (1.5–12.5 mM) were applied to in vitro slice preparations of three experimental groups of STN slices from nonlesioned control rats, ipsilateral hemispheres, and contralateral hemispheres of lesioned rats. The majority of STN neurons of nonlesioned rats and in slices contralateral to the lesion fired spontaneously, predominantly in a regular pattern, whereas those in slices ipsilateral to the lesion fired more irregularly or even in bursts. Experimentally increased [K+]o led to an increase in the number of spontaneously firing neurons and action potential firing rates in all groups. This was accompanied by a decrease in the amplitude of post spike afterhyperpolarization (AHP) and the amplitude and duration of the posttrain AHP. Lesion effects in ipsilateral neurons at physiological [K+]o resembled the effects of elevated [K+]o in nonlesioned rats. Our data suggest that changed potassium sensitivity due to conductivity alterations and delayed clearance may be critical for shaping STN activity in parkinsonian states.

Role of Potassium and Calcium in the Generation of Cellular Bursts in the Dentate Gyrus

1997 ◽  
Vol 77 (5) ◽  
pp. 2293-2299 ◽  
Author(s):  
Enhui Pan ◽  
Janet L. Stringer
Keyword(s):  
Dentate Gyrus ◽  
Granule Cells ◽  
Seizure Activity ◽  
Epileptiform Activity ◽  
Hippocampal Slices ◽  
Extracellular Potassium ◽  
Sprague Dawley

Pan, Enhui and Janet L. Stringer. Role of potassium and calcium in the generation of cellular bursts in the dentate gyrus. J. Neurophysiol. 77: 2293–2299, 1997. Epileptiform activity, which appears to be endogenous, has been recorded in the granule cells of the dentate gyrus before the onset of synchronized seizure activity and has been termed cellular bursts. It has been postulated that an increase in input to the dentate gyrus causes a local increase in extracellular K+ concentration ([K+]o) and a decrease in [Ca2+]o that results in this cellular bursting. The first test of this hypothesis is to determine whether the cellular bursts appear in ionic conditions that occur in vivo before the onset of synchronized epileptic activity. This hypothesis was tested in vitro by varying the ionic concentrations in the perfusing solution and recording changes in the granule cells of the dentate gyrus. Intra- and extracellular recordings were made in the dentate gyri of hippocampal slices prepared from anesthetized adult Sprague-Dawley rats. Increasing the extracellular potassium or decreasing the extracellular calcium of the perfusing solution caused three forms of spontaneous activity to appear: depolarizing potentials, action potentials, and cellular bursts. Increasing potassium or decreasing calcium also caused the granule cells to depolarize and reduced their input resistance. No synchronized extracellular field activity was detected. Simultaneously increasing potassium and decreasing calcium caused cellular bursts to appear at concentrations recorded in vivo before the onset of synchronized reverberatory seizure activity.

scholarly journals Lamotrigine Attenuates Neuronal Excitability, Depresses GABA Synaptic Inhibition, and Modulates Theta Rhythms in Rat Hippocampus

2021 ◽  
Author(s):  
Paulina Kazmierska-Grebowska ◽  
Marcin Siwiec ◽  
Joanna Ewa Sowa ◽  
Bartosz Caban ◽  
Tomasz Kowalczyk ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Medial Septum ◽  
Movement Planning ◽  
Theta Oscillations ◽  
Hcn Channels ◽  
Anaesthetized Rats ◽  
Hippocampal Theta

Theta oscillations generated in hippocampal (HPC) and cortical neuronal networks are involved in various aspects of brain function, including sensorimotor integration, movement planning, memory formation and attention. Disruptions of theta rhythms are present in individuals with various disorders, including epilepsy and Alzheimer’s disease. Theta rhythm generation involves a specific interplay between cellular (ionic) and network (synaptic) mechanisms. HCN channels are theta modulators, and several medications are known to enhance their activity. We investigated how different doses of lamotrigine (LTG), an HCN channel activator, and antiepileptic and neuroprotective agent, would affect hippocampal theta rhythms in acute HPC slices (in vitro) and anaesthetized rats (in vivo). Whole-cell patch clamp recordings revealed that LTG decreased GABAA-fast transmission in CA3 and CA1 cells, in vitro. In addition, LTG directly depressed CA3 and CA1 pyramidal neuron excitability. These effects were partially blocked by ZD 7288, a selective HCN blocker, and are consistent with decreased excitability associated with antiepileptic actions. Lamotrigine also depressed hippocampal theta oscillations in vitro, also consistent with its neuronal depressant effects. In contrast, it exerted an opposite, enhancing effect, on theta recorded in vivo. The contradictory in vivo and in vitro results indicate that LTG increases ascending theta activating medial septum/entorhinal synaptic inputs that over-power the depressant effects seen in hippocampal neurons. These results provide new insights into LTG actions and indicate an opportunity to develop more precise therapeutics for the treatment of dementias, memory disorders and epilepsy.

scholarly journals Lamotrigine Attenuates Neuronal Excitability, Depresses GABA Synaptic Inhibition, and Modulates Theta Rhythms in Rat Hippocampus

2021 ◽  
Vol 22 (24) ◽  
pp. 13604
Author(s):  
Paulina Kazmierska-Grebowska ◽  
Marcin Siwiec ◽  
Joanna Ewa Sowa ◽  
Bartosz Caban ◽  
Tomasz Kowalczyk ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Medial Septum ◽  
Movement Planning ◽  
Theta Oscillations ◽  
Hcn Channels ◽  
Whole Cell Patch Clamp ◽  
Anaesthetized Rats ◽  
Ca1 Pyramidal Neuron

Theta oscillations generated in hippocampal (HPC) and cortical neuronal networks are involved in various aspects of brain function, including sensorimotor integration, movement planning, memory formation and attention. Disruptions of theta rhythms are present in individuals with brain disorders, including epilepsy and Alzheimer’s disease. Theta rhythm generation involves a specific interplay between cellular (ion channel) and network (synaptic) mechanisms. HCN channels are theta modulators, and several medications are known to enhance their activity. We investigated how different doses of lamotrigine (LTG), an HCN channel modulator, and antiepileptic and neuroprotective agent, would affect HPC theta rhythms in acute HPC slices (in vitro) and anaesthetized rats (in vivo). Whole-cell patch clamp recordings revealed that LTG decreased GABAA-fast transmission in CA3 cells, in vitro. In addition, LTG directly depressed CA3 and CA1 pyramidal neuron excitability. These effects were partially blocked by ZD 7288, a selective HCN blocker, and are consistent with decreased excitability associated with antiepileptic actions. Lamotrigine depressed HPC theta oscillations in vitro, also consistent with its neuronal depressant effects. In contrast, it exerted an opposite, enhancing effect, on theta recorded in vivo. The contradictory in vivo and in vitro results indicate that LTG increases ascending theta activating medial septum/entorhinal synaptic inputs that over-power the depressant effects seen in HPC neurons. These results provide new insights into LTG actions and indicate an opportunity to develop more precise therapeutics for the treatment of dementias, memory disorders and epilepsy.

scholarly journals Compensatory mechanisms in resistant Anopheles gambiae AcerKis and KdrKis neurons modulate insecticide-based mosquito control

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Stéphane Perrier ◽  
Eléonore Moreau ◽  
Caroline Deshayes ◽  
Marine El-Adouzi ◽  
Delphine Goven ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Anopheles Gambiae ◽  
Calcium Concentration ◽  
Mosquito Control ◽  
Point Mutations ◽  
Resting Membrane Potential ◽  
Compensatory Mechanisms ◽  
Pyrethroid Insecticides

AbstractIn the malaria vector Anopheles gambiae, two point mutations in the acetylcholinesterase (ace-1R) and the sodium channel (kdrR) genes confer resistance to organophosphate/carbamate and pyrethroid insecticides, respectively. The mechanisms of compensation that recover the functional alterations associated with these mutations and their role in the modulation of insecticide efficacy are unknown. Using multidisciplinary approaches adapted to neurons isolated from resistant Anopheles gambiae AcerKis and KdrKis strains together with larval bioassays, we demonstrate that nAChRs, and the intracellular calcium concentration represent the key components of an adaptation strategy ensuring neuronal functions maintenance. In AcerKis neurons, the increased effect of acetylcholine related to the reduced acetylcholinesterase activity is compensated by expressing higher density of nAChRs permeable to calcium. In KdrKis neurons, changes in the biophysical properties of the L1014F mutant sodium channel, leading to enhance overlap between activation and inactivation relationships, diminish the resting membrane potential and reduce the fraction of calcium channels available involved in acetylcholine release. Together with the lower intracellular basal calcium concentration observed, these factors increase nAChRs sensitivity to maintain the effect of low concentration of acetylcholine. These results explain the opposite effects of the insecticide clothianidin observed in AcerKis and KdrKis neurons in vitro and in vivo.

Effect of elevated potassium on the ion content of mouse astrocytes and neurons

1992 ◽  
Vol 70 (S1) ◽  
pp. S263-S268 ◽  
Author(s):  
H. Steve White ◽  
Sien Yao Chow ◽  
Y. C. Yen-Chow ◽  
Dixon M. Woodbury
Keyword(s):  
Cortical Neurons ◽  
Cell Types ◽  
Mouse Cell ◽  
Ion Concentration ◽  
Cellular Heterogeneity ◽  
Resting Membrane Potential ◽  
Extracellular Potassium ◽  
Individual Response ◽  
Extracellular Potassium Concentration ◽  
The Brain

Potassium is tightly regulated within the extracellular compartment of the brain. Nonetheless, it can increase 3- to 4-fold during periods of intense seizure activity and 10- to 20-fold under certain pathological conditions such as spreading depression. Within the central nervous system, neurons and astrocytes are both affected by shifts in the extracellular concentration of potassium. Elevated potassium can lead to a redistribution of other ions (e.g., calcium, sodium, chloride, hydrogen, etc.) within the cellular compartment of the brain. Small shifts in the extracellular potassium concentration can markedly affect acid–base homeostasis, energy metabolism, and volume regulation of these two brain cells. Since normal neuronal function is tightly coupled to the ability of the surrounding glial cells to regulate ionic shifts within the brain and since both cell types can be affected by shifts in the extracellular potassium, it is important to characterize their individual response to an elevation of this ion. This review describes the results of side-by-side studies conducted on cortical neurons and astrocytes, which assessed the effect of elevated potassium on their resting membrane potential, intracellular volume, and their intracellular concentration of potassium, sodium, and chloride. The results obtained from these studies suggest that there exists a marked cellular heterogeneity between neurons and astrocytes in their response to an elevation in the extracellular potassium concentration.Key words: astrocytes, neurons, ion concentration, neuronal–glial interactions, mouse, cell culture.

Dorsal and Ventral Distribution of Excitable and Synaptic Properties of Neurons of the Bed Nucleus of the Stria Terminalis

2003 ◽  
Vol 90 (1) ◽  
pp. 405-414 ◽  
Author(s):  
Regula E. Egli ◽  
Danny G. Winder
Keyword(s):  
Receptor Antagonist ◽  
Drugs Of Abuse ◽  
Input Resistance ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Adult Mice ◽  
Dependent Potential

The bed nucleus of the stria terminalis (BNST) is a structure uniquely positioned to integrate stress information and regulate both stress and reward systems. Consistent with this arrangement, evidence suggests that the BNST, and in particular the noradrenergic input to this structure, is a key component of affective responses to drugs of abuse. We have utilized an in vitro slice preparation from adult mice to determine synaptic and membrane properties of these cells, focusing on the dorsal and ventral subdivisions of the anterolateral BNST (dBNST and vBNST) because of the differential noradrenergic input to these two regions. We find that while resting membrane potential and input resistance are comparable between these subdivisions, excitable properties, including a low-threshold spike (LTS) likely mediated by T-type calcium channels and an Ih-dependent potential, are differentially distributed. Inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs, respectively) are readily evoked in both dBNST and vBNST. The fast IPSP is predominantly GABAA-receptor mediated and is partially blocked by the AMPA/kainate-receptor antagonist CNQX. In the presence of the GABAA-receptor antagonist picrotoxin, cells in dBNST but not vBNST are more depolarized and have a higher input resistance, suggesting tonic GABAergic inhibition of these cells. The EPSPs elicited in BNST are monosynaptic, exhibit paired pulse facilitation, and contain both an AMPA- and an N-methyl-d-aspartate (NMDA) receptor-mediated component. These data support the hypothesis that neurons of the dorsal and ventral BNST differentially integrate synaptic input, which is likely of behavioral significance. The data also suggest mechanisms by which information may flow through stress and reward circuits.

Postnatal Changes in Membrane Properties of Mice Trigeminal Ganglion Neurons

2002 ◽  
Vol 87 (5) ◽  
pp. 2398-2407 ◽  
Author(s):  
Carmen Cabanes ◽  
Mikel López de Armentia ◽  
Félix Viana ◽  
Carlos Belmonte
Keyword(s):  
Postnatal Development ◽  
Trigeminal Ganglion ◽  
Input Resistance ◽  
Membrane Capacitance ◽  
Membrane Properties ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Depolarization Rate ◽  
Ganglion Neurons

Intracellular recordings from neurons in the mouse trigeminal ganglion (TG) in vitro were used to characterize changes in membrane properties that take place from early postnatal stages (P0–P7) to adulthood (>P21). All neonatal TG neurons had uniformly slow conduction velocities, whereas adult neurons could be separated according to their conduction velocity into Aδ and C neurons. Based on the presence or absence of a marked inflection or hump in the repolarization phase of the action potential (AP), neonatal neurons were divided into S- (slow) and F-type (fast) neurons. Their passive and subthreshold properties (resting membrane potential, input resistance, membrane capacitance, and inward rectification) were nearly identical, but they showed marked differences in AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and afterhyperpolarization (AHP) duration. Adult TG neurons also segregated into S- and F-type groups. Differences in their mean AP amplitude, AP overshoot, AP duration, rate of AP depolarization, rate of AP repolarization, and AHP duration were also prominent. In addition, axons of 90% of F-type neurons and 60% of S-type neurons became faster conducting in their central and peripheral branch, suggestive of axonal myelination. The proportion of S- and F-type neurons did not vary during postnatal development, suggesting that these phenotypes were established early in development. Membrane properties of both types of TG neurons evolved differently during postnatal development. The nature of many of these changes was linked to the process of myelination. Thus myelination was accompanied by a decrease in AP duration, input resistance ( R in), and increase in membrane capacitance (C). These properties remained constant in unmyelinated neurons (both F- and S-type). In adult TG, all F-type neurons with inward rectification were also fast-conducting Aδ, suggesting that those F-type neurons showing inward rectification at birth will evolve to F-type Aδ neurons with age. The percentage of F-type neurons showing inward rectification also increased with age. Both F- and S-type neurons displayed changes in the sensitivity of the AP to reductions in extracellular Ca2+ or substitution with Co2+ during the process of maturation.

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