scholarly journals Zonal variations in K+ currents in vestibular crista calyx terminals

2015 ◽  
Vol 113 (1) ◽  
pp. 264-276 ◽  
Author(s):  
Frances L. Meredith ◽  
Katherine J. Rennie

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.

1991 ◽  
Vol 66 (3) ◽  
pp. 744-761 ◽  
Author(s):  
S. M. Johnson ◽  
P. A. Getting

1. The purpose of this study was to determine the electrophysiological properties of neurons within the region of the nucleus ambiguus (NA), an area that contains the ventral respiratory group. By the use of an in vitro brain stem slice preparation, intracellular recordings from neurons in this region (to be referred to as NA neurons, n = 235) revealed the following properties: postinhibitory rebound (PIR), delayed excitation (DE), adaptation, and posttetanic hyperpolarization (PTH). NA neurons were separated into three groups on the basis of their expression of PIR and DE: PIR cells (58%), DE cells (31%), and Non cells (10%). Non cells expressed neither PIR nor DE and no cells expressed both PIR and DE. 2. PIR was a transient depolarization that produced a single action potential or a burst of action potentials when the cell was released from hyperpolarization. In the presence of tetrodotoxin (TTX), the maximum magnitude of PIR was 7-12 mV. Under voltage-clamp conditions, hyperpolarizing voltage steps elicited a small inward current during the hyperpolarization and a small inward tail current on release from hyperpolarization. These currents, which mediate PIR, were most likely due to Q-current because they were blocked with extracellular cesium and were insensitive to barium. 3. DE was a delay in the onset of action potential firing when cells were hyperpolarized before application of depolarizing current. When cells were hyperpolarized to -90 mV for greater than or equal to 300 ms, maximum delays ranged from 150 to 450 ms. The transient outward current underlying DE was presumed to be A-current because of the current's activation and inactivation characteristics and its elimination by 4-aminopyridine (4-AP). 4. Adaptation was examined by applying depolarizing current for 2.0 s and measuring the frequency of evoked action potentials. Although there was a large degree of variability in the degree of adaptation, PIR cells tended to express less adaptation than DE and Non cells. Nearly three-fourths of all NA neurons adapted rapidly (i.e., 50% adaptation in less than 200 ms), but PIR cells tended to adapt faster than DE and Non cells. PTH after a train of action potentials was relatively rare and occurred more often in DE cells (43%) and Non cells (33%) than in PIR cells (13%). PTH had a magnitude of up to 18 mV and time constants that reflected the presence of one (1.7 +/- 1.4 s, mean +/- SD) or two components (0.28 +/- 0.13 and 4.1 +/- 2.2 s).(ABSTRACT TRUNCATED AT 400 WORDS)


2012 ◽  
Vol 107 (6) ◽  
pp. 1718-1730 ◽  
Author(s):  
Adi Cymerblit-Sabba ◽  
Yitzhak Schiller

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.


2021 ◽  
Author(s):  
Nikollas M. Benites ◽  
Beatriz Rodrigues ◽  
Carlos H. Silveira ◽  
Ricardo M. Leão

AbstractThe dorsal cochlear nucleus (DCN) in the auditory brainstem integrates auditory and somatosensory information. Mature fusiform neurons express two qualitative intrinsic states in equal proportions: quiet, with no spontaneous regular action potential firing, or active, with regular spontaneous action potential firing. However, how these firing states and other electrophysiological properties of fusiform neurons develop during early postnatal days to adulthood is not known. Thus, we recorded fusiform neurons from mice from P4 to P21 and analyzed their electrophysiological properties. In the pre-hearing phase (P4-P13), we found that fusiform neurons are mostly quiet, with the active state emerging after hearing onset at P14. Subthreshold properties present more variations before hearing onset, while action potential properties vary more after P14, developing bigger, shorter, and faster action potentials. Interestingly, the activity threshold is more depolarized in pre-hearing cells suggesting that persistent sodium current (INaP) increases its expression after hearing. In fact, INaP increases its expression after hearing, accordingly with the development of active neurons. Thus, we suggest that the post-hearing expression of INaP creates the active state of the fusiform neuron. At the same time, other changes refine the passive membrane properties and increase the speed of action potential firing of fusiform neurons.


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Pedro L Martinez-Espinosa ◽  
Jianping Wu ◽  
Chengtao Yang ◽  
Vivian Gonzalez-Perez ◽  
Huifang Zhou ◽  
...  

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.


2017 ◽  
Author(s):  
Benoît Hastoy ◽  
Mahdieh Godazgar ◽  
Anne Clark ◽  
Vibe Nylander ◽  
Ioannis Spiliotis ◽  
...  

AbstractThe electrophysiological and secretory properties of the human β-cell lines EndoC-βH1 and EndoC-βH2 were investigated. Both cell lines respond to glucose (6-20mM) with 2-to 3-fold stimulation of insulin secretion, an effect that was mimicked by tolbutamide (0.2mM) and reversed by diazoxide (0.5mM). Glucose-induced insulin release correlated with an elevation of [Ca2+]i, membrane depolarization and increased action potential firing. KATP channel activity at 1mM glucose is low and increasing glucose to 6 or 20mM reduced KATP channel activity to the same extent as application of the KATP channel blocker tolbutamide (0.2mM). The upstroke of the action potentials in EndoC-βH1 and −βH2 cells observed at high glucose principally reflects activation of L- and P/Q-type Ca2+ channels with some small contribution of TTX-sensitive Na+ channels. Action potential repolarization involves activation of voltage-gated Kv2.2 channels and large-conductance Ca2+-activated K+ channels. Exocytosis (measured by measurements of membrane capacitance) was triggered by membrane depolarizations >10ms to membrane potentials above -30mV. Both cell lines were well-granulated (6,000-15,000 granules/cell) and granules consisted of a central insulin core surrounded by a clear halo. We conclude that the EndoC-βH1 and -βH2 cells share many features of primary human β-cells and that they represent a useful experimental model.


2020 ◽  
Author(s):  
Martin Loynaz Prieto ◽  
Kamyar Firouzi ◽  
Butrus T. Khuri-Yakub ◽  
Daniel V. Madison ◽  
Merritt Maduke

ABSTRACTUltrasound can modulate action-potential firing in vivo and in vitro, but the mechanistic basis of this phenomenon is not well understood. To address this problem, we used patch-clamp recording to quantify the effects of focused, high-frequency (43 MHz) ultrasound on evoked action potential firing in CA1 pyramidal neurons in acute rodent hippocampal brain slices. We find that ultrasound can either inhibit or potentiate firing in a spike-frequency-dependent manner: at low (near-threshold) input currents and low firing frequencies, ultrasound inhibits firing, while at higher input currents and higher firing frequencies, ultrasound potentiates firing. The net result of these two competing effects is that ultrasound increases the threshold current for action potential firing, the slope of frequency-input curves, and the maximum firing frequency. In addition, ultrasound slightly hyperpolarizes the resting membrane potential, decreases action potential width, and increases the depth of the afterhyperpolarization. All of these results can be explained by the hypothesis that ultrasound activates a sustained potassium conductance. According to this hypothesis, increased outward potassium currents hyperpolarize the resting membrane potential and inhibit firing at near-threshold input currents, but potentiate firing in response to higher input currents by limiting inactivation of voltage-dependent sodium channels during the action potential. This latter effect is a consequence of faster action-potential repolarization, which limits inactivation of voltage-dependent sodium channels, and deeper (more negative) afterhyperpolarization, which increases the rate of recovery from inactivation. Based on these results we propose that ultrasound activates thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels, through heating or mechanical effects of acoustic radiation force. Finite-element modelling of the effects of ultrasound on brain tissue suggests that the effects of ultrasound on firing frequency are caused by a small (less than 2°C) increase in temperature, with possible additional contributions from mechanical effectsSUMMARYPrieto et al. describe how ultrasound can either inhibit or potentiate action potential firing in hippocampal pyramidal neurons and demonstrate that these effects can be explained by increased potassium conductance.


2020 ◽  
Vol 152 (11) ◽  
Author(s):  
Martin Loynaz Prieto ◽  
Kamyar Firouzi ◽  
Butrus T. Khuri-Yakub ◽  
Daniel V. Madison ◽  
Merritt Maduke

Ultrasound can modulate action potential firing in vivo and in vitro, but the mechanistic basis of this phenomenon is not well understood. To address this problem, we used patch-clamp recording to quantify the effects of focused, high-frequency (43 MHz) ultrasound on evoked action potential firing in CA1 pyramidal neurons in acute rodent hippocampal brain slices. We find that ultrasound can either inhibit or potentiate firing in a spike frequency–dependent manner: at low (near-threshold) input currents and low firing frequencies, ultrasound inhibits firing, while at higher input currents and higher firing frequencies, ultrasound potentiates firing. The net result of these two competing effects is that ultrasound increases the threshold current for action potential firing, the slope of frequency-input curves, and the maximum firing frequency. In addition, ultrasound slightly hyperpolarizes the resting membrane potential, decreases action potential width, and increases the depth of the after-hyperpolarization. All of these results can be explained by the hypothesis that ultrasound activates a sustained potassium conductance. According to this hypothesis, increased outward potassium currents hyperpolarize the resting membrane potential and inhibit firing at near-threshold input currents but potentiate firing in response to higher-input currents by limiting inactivation of voltage-dependent sodium channels during the action potential. This latter effect is a consequence of faster action potential repolarization, which limits inactivation of voltage-dependent sodium channels, and deeper (more negative) after-hyperpolarization, which increases the rate of recovery from inactivation. Based on these results, we propose that ultrasound activates thermosensitive and mechanosensitive two-pore-domain potassium (K2P) channels through heating or mechanical effects of acoustic radiation force. Finite-element modeling of the effects of ultrasound on brain tissue suggests that the effects of ultrasound on firing frequency are caused by a small (<2°C) increase in temperature, with possible additional contributions from mechanical effects.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2686
Author(s):  
Gerrit C. Beekhof ◽  
Simona V. Gornati ◽  
Cathrin B. Canto ◽  
Avraham M. Libster ◽  
Martijn Schonewille ◽  
...  

Purkinje cells (PCs) in the cerebellar cortex can be divided into at least two main subpopulations: one subpopulation that prominently expresses ZebrinII (Z+), and shows a relatively low simple spike firing rate, and another that hardly expresses ZebrinII (Z–) and shows higher baseline firing rates. Likewise, the complex spike responses of PCs, which are evoked by climbing fiber inputs and thus reflect the activity of the inferior olive (IO), show the same dichotomy. However, it is not known whether the target neurons of PCs in the cerebellar nuclei (CN) maintain this bimodal distribution. Electrophysiological recordings in awake adult mice show that the rate of action potential firing of CN neurons that receive input from Z+ PCs was consistently lower than that of CN neurons innervated by Z– PCs. Similar in vivo recordings in juvenile and adolescent mice indicated that the firing frequency of CN neurons correlates to the ZebrinII identity of the PC afferents in adult, but not postnatal stages. Finally, the spontaneous action potential firing pattern of adult CN neurons recorded in vitro revealed no significant differences in intrinsic pacemaking activity between ZebrinII identities. Our findings indicate that all three main components of the olivocerebellar loop, i.e., PCs, IO neurons and CN neurons, operate at a higher rate in the Z– modules.


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