scholarly journals Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis

2012 ◽  
Vol 302 (1) ◽  
pp. G176-G181 ◽  
Author(s):  
Yaohui Zhu ◽  
Kshama Mehta ◽  
Cuiping Li ◽  
Guang-Yin Xu ◽  
Liansheng Liu ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Sensory Neurons ◽  
Neuronal Excitability ◽  
Potassium Currents ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Trinitrobenzene Sulfonic Acid ◽  
Mrna Levels ◽  
Control Serum ◽  
Clamp Condition

We have previously shown that pancreatic sensory neurons in rats with chronic pancreatitis (CP) display increased excitability associated with a decrease in transient inactivating potassium currents ( IA), thus accounting in part for the hyperalgesia associated with this condition. Because of its well known role in somatic hyperalgesia, we hypothesized a role for the nerve growth factor (NGF) in driving these changes. CP was induced by intraductal injection of trinitrobenzene sulfonic acid (TNBS) in rats. After 3 wk, anti-NGF antibody or control serum was injected intra-peritoneally daily for 1 wk. This protocol was repeated in another set of experiments in control rats (receiving intraductal PBS instead of TNBS). Pancreatic nociceptors labeled with the dye Dil were identified, and patch-clamp recordings were made from acutely dissociated DRG neurons. Sensory neurons from anti-NGF-treated rats displayed a lower resting membrane potential, increased rheobase, decreased burst discharges in response to stimulatory current, and decreased input resistance compared with those treated with control serum. Under voltage-clamp condition, neuronal IA density was increased in anti-NGF-treated rats compared with rats treated with control serum. However, anti-NGF treatment had no effect on electrophysiological parameters in neurons from control rats. The expression of Kv-associated channel or ancillary genes Kv1.4, 4.1, 4.2, 4.3, and DPP6, DPP10, and KCHIPs 1–4 in pancreas-specific nociceptors was examined by laser-capture microdissection and real-time PCR quantification of mRNA levels. No significant differences were seen among those. These findings emphasize a key role for NGF in maintaining neuronal excitability in CP specifically via downregulation of IA by as yet unknown mechanisms.

Electrotonic structure of olfactory sensory neurons analyzed by intracellular and whole cell patch techniques

1991 ◽  
Vol 65 (3) ◽  
pp. 747-758 ◽  
Author(s):  
F. Pongracz ◽  
S. Firestein ◽  
G. M. Shepherd
Keyword(s):  
Sensory Neurons ◽  
Information Transfer ◽  
Experimental Studies ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Ambystoma Tigrinum ◽  
Olfactory Sensory Neurons ◽  
Isolated Cells ◽  
Whole Cell

1. Experimental studies employing whole cell patch recordings from freshly isolated olfactory sensory neurons of the salamander (Ambystoma tigrinum) yield much higher estimates of specific membrane resistance (Rm) than studies using conventional intracellular recordings from in situ neurons. Because Rm is critical for understanding information transfer in these cells, we have used computational methods to analyze the possible reasons for this difference. 2. Compartmental models were constructed for both the in situ and isolated neurons, using SABER, a general-purpose simulation program. For Rm in the in situ cell, we used a high value of 100,000 omega.cm2, as estimated in the whole cell recordings from isolated cells. A shunt across the cell membrane caused by the penetrating microelectrode was simulated by several types of shunt mechanisms, and its effects on lowering the apparent value of resting membrane potential (MP), input resistance (RN), and membrane time constant (tau m) and increasing the electrotonic length (L) were analyzed. 3. A good approximation of the electrotonic properties recorded intracellularly was obtained in the in situ model with high Rm combined with an electrode shunt consisting of Na and K conductances. A raised K conductance (1-5 nS) helps to maintain the resting MP while contributing to the increased conductance, which lowers RN and shortens the apparent tau m toward the experimental values. 4. Combined shunt resistances of 0.1-0.2 G omega (5-10 nS) gave the best fits with the experimental data. These shunts were two to three orders of magnitude smaller than the values reported from intracellular penetrations in muscle cells and motoneurons. This may be correlated with the smaller electrode tips used in the recordings from these small neurons. We thus confirm the prediction that even small values of electrode shunt have relatively large effects on the recorded electrotonic properties of small neurons, because of their high RN (2-5 G omega). 5. We have further explored the effects on electrotonic structure of a nonuniform Rm by giving higher Rm values to the distally located cilia compared with the proximal soma-dendritic region, as indicated by recent experiments. For the same RN, large increases in ciliary Rm above 100,000 omega.cm2 can be balanced by relatively small decreases below that value in soma-dendritic Rm. A high ciliary Rm appears to be a specialization for transduction of the sensory input, as reported also in photoreceptors and hair cells.

scholarly journals Melatonin Reduces Excitability in Dorsal Root Ganglia Neurons with Inflection on the Repolarization Phase of the Action Potential

2019 ◽  
Vol 20 (11) ◽  
pp. 2611 ◽  
Author(s):  
Klausen Oliveira-Abreu ◽  
Nathalia Silva-dos-Santos ◽  
Andrelina Coelho-de-Souza ◽  
Francisco Ferreira-da-Silva ◽  
Kerly Silva-Alves ◽  
...  
Keyword(s):  
Action Potential ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Neuronal Excitability ◽  
Input Resistance ◽  
Cell Types ◽  
Neuronal Population ◽  
Resting Membrane Potential ◽  
Electrophysiological Properties ◽  
Repolarization Phase

Melatonin is a neurohormone produced and secreted at night by pineal gland. Many effects of melatonin have already been described, for example: Activation of potassium channels in the suprachiasmatic nucleus and inhibition of excitability of a sub-population of neurons of the dorsal root ganglia (DRG). The DRG is described as a structure with several neuronal populations. One classification, based on the repolarizing phase of the action potential (AP), divides DRG neurons into two types: Without (N0) and with (Ninf) inflection on the repolarization phase of the action potential. We have previously demonstrated that melatonin inhibits excitability in N0 neurons, and in the present work, we aimed to investigate the melatonin effects on the other neurons (Ninf) of the DRG neuronal population. This investigation was done using sharp microelectrode technique in the current clamp mode. Melatonin (0.01–1000.0 nM) showed inhibitory activity on neuronal excitability, which can be observed by the blockade of the AP and by the increase in rheobase. However, we observed that, while some neurons were sensitive to melatonin effect on excitability (excitability melatonin sensitive—EMS), other neurons were not sensitive to melatonin effect on excitability (excitability melatonin not sensitive—EMNS). Concerning the passive electrophysiological properties of the neurons, melatonin caused a hyperpolarization of the resting membrane potential in both cell types. Regarding the input resistance (Rin), melatonin did not change this parameter in the EMS cells, but increased its values in the EMNS cells. Melatonin also altered several AP parameters in EMS cells, the most conspicuously changed was the (dV/dt)max of AP depolarization, which is in coherence with melatonin effects on excitability. Otherwise, in EMNS cells, melatonin (0.1–1000.0 nM) induced no alteration of (dV/dt)max of AP depolarization. Thus, taking these data together, and the data of previous publication on melatonin effect on N0 neurons shows that this substance has a greater pharmacological potency on Ninf neurons. We suggest that melatonin has important physiological function related to Ninf neurons and this is likely to bear a potential relevant therapeutic use, since Ninf neurons are related to nociception.

Chronic High-Inspired CO2 Decreases Excitability of Mouse Hippocampal Neurons

2007 ◽  
Vol 97 (2) ◽  
pp. 1833-1838 ◽  
Author(s):  
Xiang Q. Gu ◽  
Amjad Kanaan ◽  
Hang Yao ◽  
Gabriel G. Haddad
Keyword(s):  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Channel Current ◽  
Conductance Curve ◽  
Recovery From Inactivation ◽  
Channel Expression ◽  
Steady State Inactivation ◽  
And Function

To examine the effect of chronically elevated CO2 on excitability and function of neurons, we exposed mice to 8 and 12% CO2 for 4 wk (starting at 2 days of age), and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Chronic CO2-treated neurons (CC) had a similar input resistance ( Rm) and resting membrane potential ( Vm) as control (CON). Although treatment with 8% CO2 did not change the rheobase (64 ± 11 pA, n = 9 vs. 47 ± 12 pA, n = 8 for CC 8% vs. CON; means ± SE), 12% CO2 treatment increased it significantly (73 ± 8 pA, n = 9, P = 0.05). Furthermore, the 12% CO2 but not the 8% CO2 treatment decreased the Na+ channel current density (244 ± 36 pA/pF, n = 17, vs. 436 ± 56 pA/pF, n = 18, for CC vs. CON, P = 0.005). Recovery from inactivation was also lowered by 12% but not 8% CO2. Other gating properties of Na+ current, such as voltage-conductance curve, steady-state inactivation, and time constant for deactivation, were not modified by either treatment. Western blot analysis showed that the expression of Na+ channel types I–III was not changed by 8% CO2 treatment, but their expression was significantly decreased by 20–30% ( P = 0.03) by the 12% treatment. We conclude from these data and others that neuronal excitability and Na+ channel expression depend on the duration and level of CO2 exposure and maturational changes occur in early life regarding neuronal responsiveness to CO2.

Patch-Clamp Analysis of Gene-Targeted Vomeronasal Neurons Expressing a Defined V1r or V2r Receptor: Ionic Mechanisms Underlying Persistent Firing

2007 ◽  
Vol 98 (4) ◽  
pp. 2357-2369 ◽  
Author(s):  
Kirill Ukhanov ◽  
Trese Leinders-Zufall ◽  
Frank Zufall
Keyword(s):  
Sensory Neurons ◽  
Cell Damage ◽  
Critical Role ◽  
Vomeronasal Organ ◽  
Input Resistance ◽  
Cell Types ◽  
Brain Regions ◽  
Resting Membrane Potential ◽  
Action Potential Firing ◽  
Persistent Firing

Sensory neurons in the mouse vomeronasal organ consist of two major groups, apical and basal, that project to different brain regions, express unique sets of receptors, and serve distinct functions. Electrical properties of these two subpopulations, however, have not been systematically characterized. V1rb2-tau-GFP and V2r1b-tau-GFP tagged vomeronasal sensory neurons (VSNs) were selected as prototypical apical or basal VSNs, respectively, and their biophysical properties were analyzed in acute slices that minimized cell damage. Basal V2r1b-expressing VSNs had voltage-gated conductances, and especially Na+ (Nav) and Ca2+ (Cav) currents, that were substantially larger than those observed in apical V1rb2 VSNs, although the resting membrane potential, input resistance, and membrane capacitance were similar in both cell types. Of several types of Cav currents, T-type and L-type Cav currents contributed to action potential firing, and both currents alone were capable of generating oscillatory Ca2+ spikes. The L-type Cav current was uniquely coupled to a BK large-conductance K+ current, and interplay between these channels played a critical role in repolarizing spikes and maintaining persistent firing in VSNs. Larger Nav and Cav conductances, along with a more positive inactivation voltage of the Nav current in the V2r1b VSNs, contributed to the larger spike amplitude and higher spike frequency induced by depolarizing current in these cells compared with V1rb2 VSNs. Basal GFP-negative VSNs and V2r1b VSNs responded to prolonged depolarization with persistent, but adapting discharge that could be relevant in sensory adaptation. Collectively, these results suggest a novel mechanism for regulating and encoding neuronal activity in the accessory olfactory system.

scholarly journals Hyperexcitability of Sensory Neurons in Fragile X Mouse Model

2021 ◽  
Vol 14 ◽  
Author(s):  
Pan-Yue Deng ◽  
Oshri Avraham ◽  
Valeria Cavalli ◽  
Vitaly A. Klyachko
Keyword(s):  
Mouse Model ◽  
Sensory Neuron ◽  
Sensory Neurons ◽  
Fragile X ◽  
Input Resistance ◽  
Resting Membrane Potential ◽  
Hcn Channels ◽  
Satellite Glial Cells ◽  
Peripheral Sensory Neurons ◽  
Peripheral Sensory

Sensory hypersensitivity and somatosensory deficits represent the core symptoms of Fragile X syndrome (FXS). These alterations are believed to arise from changes in cortical sensory processing, while potential deficits in the function of peripheral sensory neurons residing in dorsal root ganglia remain unexplored. We found that peripheral sensory neurons exhibit pronounced hyperexcitability in Fmr1 KO mice, manifested by markedly increased action potential (AP) firing rate and decreased threshold. Unlike excitability changes found in many central neurons, no significant changes were observed in AP rising and falling time, peak potential, amplitude, or duration. Sensory neuron hyperexcitability was caused primarily by increased input resistance, without changes in cell capacitance or resting membrane potential. Analyses of the underlying mechanisms revealed reduced activity of HCN channels and reduced expression of HCN1 and HCN4 in Fmr1 KO compared to WT. A selective HCN channel blocker abolished differences in all measures of sensory neuron excitability between WT and Fmr1 KO neurons. These results reveal a hyperexcitable state of peripheral sensory neurons in Fmr1 KO mice caused by dysfunction of HCN channels. In addition to the intrinsic neuronal dysfunction, the accompanying paper examines deficits in sensory neuron association/communication with their enveloping satellite glial cells, suggesting contributions from both neuronal intrinsic and extrinsic mechanisms to sensory dysfunction in the FXS mouse model.

TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons

2002 ◽  
Vol 282 (6) ◽  
pp. G1045-G1051 ◽  
Author(s):  
Beverley A. Moore ◽  
Timothy M. R. Stewart ◽  
Ceredwyn Hill ◽  
Stephen J. Vanner
Keyword(s):  
Action Potential ◽  
Intestinal Inflammation ◽  
Input Resistance ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Cell Diameter ◽  
Trinitrobenzene Sulfonic Acid ◽  
Drg Neurons ◽  
Nociceptive Neurons ◽  
Electrophysiological Properties

This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular recording techniques were used to measure electrophysiological properties of acutely dissociated neurons 12–24 h after dissection. Nociceptive neurons were identified by sensitivity to capsaicin, tetrodotoxin resistance, and size (<30 μm). The action potential threshold in neurons from TNBS-treated animals was reduced by >70% compared with controls ( P < 0.001), but the resting membrane potential was unchanged. Cell diameter, input resistance (67%), and action potential upstroke velocity (22%) increased in the TNBS group ( P < 0.05). The number of action potentials discharged increased in the TNBS group ( P < 0.001), whereas application of 4-aminopyridine to control cells mimicked this effect. This study demonstrates that ileitis induces hyperexcitability in nociceptive DRG neurons and changes in the properties of Na+ and K+channels at the soma, which persist after removal from the inflamed environment.

Activation of NMDA receptor-channels in human retinal Müller glial cells inhibits inward-rectifying potassium currents

1996 ◽  
Vol 13 (2) ◽  
pp. 319-326 ◽  
Author(s):  
Donald G. Puro ◽  
Joseph P. Yuan ◽  
Nikolaus J. Sucher
Keyword(s):  
Nmda Receptor ◽  
Glial Cells ◽  
Neuronal Excitability ◽  
Müller Cells ◽  
Potassium Currents ◽  
Inhibitory Effect ◽  
Resting Membrane Potential ◽  
Bathing Solution ◽  
Dependent Manner ◽  
Muller Cells

AbstractAlthough it is well known that neurotransmitters mediate neuron-to-neuron communication, it is becoming clear that neurotransmitters also affect glial cells. However, knowledge of neuron-to-glial signalling is limited. In this study, we examined the effects of the glutamate agonist N-methyl-D-aspartate (NMDA) on Müller cells, the predominant glia of the retina. Our immunocytochemical studies and immunodetection by Western blotting with monoclonal antibodies specific for the NMDAR1 subunit provided evidence for the expression by human Müller cells of this essential component of NMDA receptor-channels. Under conditions in which potassium currents were blocked, NMDA-induced currents could be detected in perforated-patch recordings from cultured and freshly dissociated human Müller cells. These currents were inhibited by competitive and non-competitive blockers of NMDA receptor-channels. Extracellular magnesium reduced the NMDA-activated currents in a voltage-dependent manner. However, despite a partial block by magnesium, Müller cells remained responsive to NMDA at the resting membrane potential. Under assay conditions not blocking K+ currents, exposure of Müller cells to NMDA was associated with an MK-801 sensitive inhibition of the inward-rectifying K+ current (IK(IR)), the largest current of these glia. This inhibitory effect of NMDA appears to be mediated by an influx of calcium since the inhibition of IK(IR) was significantly reduced when calcium was removed from the bathing solution or when the Müller cells contained the calcium chelator, BAPTA. Inhibition of the Müller cell KIR channels by the neurotransmitter glutamate is likely to have significant functional consequences for the retina since these ion channels are involved in K+ homeostasis, which in turn influences neuronal excitability.

scholarly journals Manipulation of the Potassium Channel Kv1.1 and Its Effect on Neuronal Excitability in Rat Sensory Neurons

2007 ◽  
Vol 98 (5) ◽  
pp. 2683-2692 ◽  
Author(s):  
Xian Xuan Chi ◽  
G. D. Nicol
Keyword(s):  
Potassium Channel ◽  
Sensory Neurons ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Small Diameter ◽  
Resting Membrane Potential ◽  
Functional Protein ◽  
Western Blots ◽  
Firing Threshold ◽  
Sirna Treatment

Potassium channels play a critical role in regulating many aspects of action potential (AP) firing. To establish the contribution of the voltage-dependent potassium channel Kv1.1 in regulating excitability, we used the selective blocker dendrotoxin-K (DTX-K) and small interfering RNA (siRNA) targeted to Kv1.1 to determine their effects on AP firing in small-diameter capsaicin-sensitive sensory neurons. A 5-min exposure to 10 nM DTX-K suppressed the total potassium current ( IK) measured at +40 mV by about 33%. DTX-K produced a twofold increase in the number of APs evoked by a ramp of depolarizing current. Associated with increased firing was a decrease in firing threshold and rheobase. DTX-K did not alter the resting membrane potential or the AP duration. A 48-h treatment with siRNA targeted to Kv1.1 reduced the expression of this channel protein by about 60% as measured in Western blots. After treatment with siRNA, IK was no longer sensitive to DTX-K, indicating a loss of functional protein. Similarly, after siRNA treatment exposure to DTX-K had no effect on the number of evoked APs, firing threshold, or rheobase. However, after siRNA treatment, the firing threshold had values similar to those obtained after acute exposure to DTX-K, suggesting that the loss of Kv1.1 plays a critical role in setting this parameter of excitability. These results demonstrate that Kv1.1 plays an important role in limiting AP firing and that siRNA may be a useful approach to establish the role of specific ion channels in the absence of selective antagonists.

scholarly journals Μελέτη της διεγερσιμότητας των πυραμιδοειδών νευρώνων της περιοχής CA1 του ιπποκάμπου

2003 ◽  
Author(s):  
Γκρέτα Βόζνιακ
Keyword(s):  
Current Pulse ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Epileptiform Activity ◽  
Input Resistance ◽  
Longitudinal Axis ◽  
Functional Differentiation ◽  
Membrane Properties ◽  
Resting Membrane Potential ◽  
Firing Characteristics

Recent reports have acknowledged the existence of functional differentiation along the longitudinal axis of the hippocampus, the ventral part being more prone to epileptogenesis. The aim of the present study was to investigate the membrane properties and firing characteristics of principal neurons of dorsal (DH) and ventral hippocampus (VH) that might account for this differentiation. Intracellular recordings were made from CA1 pyramidal neurons of DH and VH hippocampus. Resting membrane potential (DH: -64,17±0,65mV; VH: -63,84±0,82mV), input resistance (DH: 45,92±4,99ΜΩ; VH: 46,28±6,24ΜΩ), and time constant (DH: 22,11 ±1,13ms; VH: 19,32±0,87ms) did not differ between DH (n=21 and VH (n=12) neurons. Action potential (AP) parameters were measured from single AP's elicited by brief current pulse (3-1 Oms) in DH (n=7) and VH (n=7) neurons. Peak amplitude (DH: 89,71±1,99mV; VH: 80,57±1,92 mV), rise time (DH: 0,22±0,01ms; VH: 0,21±0,01ms), decay time (DH: 0,97±0,02ms: VH: 0,98±0,02ms), half width (DH: 1,31±0,07ms; VH: 1,14 ±0,03ms). However, fast afterhyperpolarizations (fAHP) following AP’s were significantly weaker in VH (-4,07±0,7mV) compared to DH (-7,53±1,16mV) neurons (p<0,05). Moreover, the 1st interspike interval (ISI; DH: 4,9±0,34ms, n=25; VH: 3,9±0,3ms, n=15) of a train of AP’s elicited by a depolarizing current pulse (500ms, 0.4nA), as well as the number of AP’s within the pulse (DH: 6,8±0,9; VH: 12,1 ±0,2), was significantly different between the two groups of neurons (p<0,05). The data suggest that the weaker fAHP in VH could underlie its higher neuronal excitability as expressed by the shorter ISI. These finding confirm and extend previous evidence for functional differentiation between DH and VH and explain, to some extend, the relatively higher tendency of VH toward epileptiform activity.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

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