scholarly journals Excitatory GABAergic modulation of calyx terminals in the vestibular sensory end organ

2020 ◽  
Author(s):  
Yugandhar Ramakrishna ◽  
Soroush G. Sadeghi
Keyword(s):  
Action Potential ◽  
Gaba Receptors ◽  
Extracellular Fluid ◽  
Potassium Currents ◽  
Spontaneous Discharge ◽  
Sprague Dawley ◽  
Patch Clamp Recording ◽  
Excitatory Effect ◽  
Action Potential Firing ◽  
Single Action

ABSTRACTGABAergic sources have been identified in the vestibular sensory neuroepithelium, mainly in the supporting cells. However, existence of GABA receptors or any possible GABAergic effects on vestibular nerve afferents has not been investigated. The current study was conducted to determine whether activation of GABA-B receptors affects calyx afferent terminals in the central region of the cristae of the semicircular canals in rats. We used patch clamp recording in P13 – P18 Sprague-Dawley rats of either sex. Application of GABA-B receptor agonist baclofen inhibited voltage activated outward potassium currents. This effect was blocked by selective GABA-B receptor antagonist CGP 35348. Antagonists of small (SK) and large (BK) current potassium channels resulted in an almost complete block of baclofen effect. The remaining baclofen effect was due to inhibition of voltage gated calcium channels and was blocked by cadmium chloride. Furthermore, baclofen had no effect in the absence of calcium in the extracellular fluid. Inhibition of potassium currents by GABA-B activation resulted in an excitatory effect on calyx terminal action potential firing. While in the control condition calyces could only fire a single action potential during step depolarizations, in the presence of baclofen they fired continuously during steps and a few even showed spontaneous discharge. We also found a decrease in threshold for action potential generation and a decrease in first spike latency during step depolarization. These results provide the first evidence for the presence of GABA-B receptors on calyx terminals, show that their activation results in an unusual excitatory effect and that GABA inputs could be used to modulate calyx response properties.

Electrophysiological properties of neurons within the nucleus ambiguus of adult guinea pigs

1991 ◽  
Vol 66 (3) ◽  
pp. 744-761 ◽  
Author(s):  
S. M. Johnson ◽  
P. A. Getting
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Nucleus Ambiguus ◽  
Transient Outward Current ◽  
Maximum Magnitude ◽  
Action Potential Firing ◽  
Onset Of Action ◽  
Electrophysiological Properties ◽  
Single Action

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)

scholarly journals Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation

2012 ◽  
Vol 302 (7) ◽  
pp. G740-G747 ◽  
Author(s):  
Galya R. Abdrakhmanova ◽  
Minho Kang ◽  
M. Imad Damaj ◽  
Hamid I. Akbarali
Keyword(s):  
Mouse Model ◽  
Action Potential ◽  
Action Potentials ◽  
Drg Neurons ◽  
Action Potential Firing ◽  
Colonic Inflammation ◽  
Single Action ◽  
Nicotine Administration ◽  
Potential Firing

Recently, we reported that nicotine in vitro at a low 1-μM concentration suppresses hyperexcitability of colonic dorsal root ganglia (DRG; L1-L2) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation ( 1 ). Here we show that multiple action potential firing in colonic DRG neurons persisted at least for 3 wk post-DSS administration while the inflammatory signs were diminished. Similar to that in DSS-induced acute colitis, bath-applied nicotine (1 μM) gradually reduced regenerative multiple-spike action potentials in colonic DRG neurons to a single action potential in 3 wk post-DSS neurons. Nicotine (1 μM) shifted the activation curve for tetrodotoxin (TTX)-resistant sodium currents in inflamed colonic DRG neurons (voltage of half-activation changed from −37 to −32 mV) but did not affect TTX-sensitive currents in control colonic DRG neurons. Further, subcutaneous nicotine administration (2 mg/kg b.i.d.) in DSS-treated C57Bl/J6 male mice resulted in suppression of hyperexcitability of colonic DRG (L1-L2) neurons and the number of abdominal constrictions in response to intraperitoneal injection of 0.6% acetic acid. Collectively, the data suggest that neuronal nicotinic acetylcholine receptor-mediated suppression of hyperexcitability of colonic DRG neurons attenuates reduction of visceral hypersensitivity in DSS mouse model of colonic inflammation.

scholarly journals Histamine-Induced Excitatory Responses in Mouse Ventromedial Hypothalamic Neurons: Ionic Mechanisms and Estrogenic Regulation

2007 ◽  
Vol 98 (6) ◽  
pp. 3143-3152 ◽  
Author(s):  
Jin Zhou ◽  
Anna W. Lee ◽  
Nino Devidze ◽  
Qiuyu Zhang ◽  
Lee-Ming Kow ◽  
...  
Keyword(s):  
Action Potential ◽  
Brain Slices ◽  
Histamine Receptor ◽  
Ventromedial Hypothalamus ◽  
Patch Clamp Recording ◽  
Action Potential Firing ◽  
Inward Current ◽  
Ovariectomized Mice ◽  
Ionic Mechanisms ◽  
The Impact

Histamine is capable of modulating CNS arousal states by regulating neuronal excitability. In the current study, histamine action in the ventromedial hypothalamus (VMH), its related ionic mechanisms, and its possible facilitation by estrogen were investigated using whole cell patch-clamp recording in brain slices from ovariectomized female mice. Under current clamp, a bath application of histamine (20 μM) caused membrane depolarization, associated with an increased membrane resistance. In some cells, the depolarization was accompanied by action potentials. Histamine application also significantly reduced the latency of action potential evoked by current steps. Histamine-induced depolarization was not affected by either tetrodotoxin or Cd2+. However, after blocking K+ channels with tetraethylammonium, 4-aminopyridine, and Cs+, depolarization was significantly decreased. Under voltage clamp, histamine-induced depolarization was associated with an inward current. The current–voltage relationship revealed that this inward current reversed near EK. The histamine effect was mimicked by a histamine receptor 1 (H1) agonist, but not a histamine receptor 2 (H2) agonist. An H1 antagonist, but not H2 antagonist, abolished histamine responses. When ovariectomized mice were treated with estradiol benzoate (E2), histamine-induced depolarization was significantly enhanced with an increased percentage of cells showing action potential firing. These results suggest that histamine depolarized VMH neurons by attenuating a K+ leakage current and this effect was mediated by H1 receptor. E2 facilitated histamine-induced excitation of VMH neurons. This histamine effect may present a potential mechanism by which estrogens modulate the impact of generalized CNS arousal on a sexual arousal–related neuronal group.

scholarly journals Effects of Divalent Cations on Outward Potassium Currents in Leech Retzius Nerve Cells

2016 ◽  
Vol 17 (4) ◽  
pp. 309-314
Author(s):  
Zorica Jovanovic ◽  
Olgica Mihaljevic ◽  
Irena Kostic
Keyword(s):  
Action Potential ◽  
Neuronal Excitability ◽  
Divalent Cations ◽  
Extracellular Fluid ◽  
Outward Current ◽  
Potassium Currents ◽  
Nerve Cells ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Retzius Cells

Abstract The present study examines the effects of divalent metals, cadmium (Cd2+) and manganese (Mn2+), on the outward potassium currents of Retzius cells in the hirudinid leeches Haemopis sanguisuga using conventional two-microelectrode voltageclamp techniques. The outward potassium current is activated by depolarization and plays an important role in determining both the neuronal excitability and action potential duration. A strong inhibition of the fast current and a clear reduction in the late currents of the outward current with 1 mM Cd2+ were obtained, which indicated that both components are sensitive to this metal. Complete blockage of the fast and partial reduction of the slow outward currents was observed after adding 1 mM Mn2+ to the extracellular fluid. These data show that the outward K+ current in leech Retzius nerve cells comprises at least two components: a voltage-dependent K+ current and a Ca2+- activated K+ current. These observations also indicate that Cd2+ is more eff ective than Mn2+ in blocking ion fl ow through these channels and that suppressing Ca2+-activated K+ outward currents can prolong the action potential in nerve cells.

scholarly journals The anesthetic bupivacaine induces cardiotoxicity by targeting L-type voltage-dependent calcium channels

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094261
Author(s):  
YaNan Gao ◽  
Bo Chen ◽  
Xue Zhang ◽  
Rui Yang ◽  
QingLi Hua ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Neonatal Rat ◽  
Sprague Dawley ◽  
Patch Clamp Recording ◽  
Drug Induced ◽  
Multifunctional Protein ◽  
Ventricular Cells ◽  
Sprague Dawley Rats ◽  
Voltage Dependent

Objective Bupivacaine is an amide local anesthetic with possible side effects that include an irregular heart rate. However, the mechanism of bupivacaine-induced cardiotoxicity has not been fully elucidated, thus we aimed to examine this mechanism. Methods We performed electrocardiogram recordings to detect action potential waveforms in Sprague Dawley rats after application of bupivacaine, while calcium (Ca2+) currents in neonatal rat ventricular cells were examined by patch clamp recording. Western blot and quantitative real-time polymerase chain reaction assays were used to detect the expression levels of targets of interest. Results In the present study, after application of bupivacaine, abnormal action potential waveforms were detected in Sprague Dawley rats by electrocardiogram recordings, while decreased Ca2+ currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of CaV1.3 (L-type) Ca2+ channels, which may be regulated by the multifunctional protein calreticulin. Conclusions The present study identifies a possible role of the calreticulin–CaV1.3 axis in bupivacaine-induced abnormal action potentials and Ca2+ currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.

scholarly journals Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Matthias Kreuzer ◽  
Paul S. García ◽  
Verena Brucklacher-Waldert ◽  
Rebecca Claassen ◽  
Gerhard Schneider ◽  
...  
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Spectral Power ◽  
Spectral Composition ◽  
Field Potential ◽  
Cortical Network ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Action Potential Firing ◽  
Experimental Conditions

Abstract Background The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic and sedative-hypnotic effects. Although each of these molecules effectively reduce the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method We used electrophysiological recordings from organotypic slice cultures derived from Sprague–Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM, n = 7) or ethanol (30 and 60 mM, n = 11) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results While both substances seem to decrease neocortical action potential firing in a not significantly different (p = 0.659, Mann–Whitney U) fashion, diazepam increases the spectral power of the up-state without significantly impacting the spectral composition, whereas ethanol does not significantly change the spectral power but the oscillatory architecture of the up-state as revealed by the Friedman test with Bonferroni correction (p < 0.05). Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam for a wide frequency range and a narrow-band de-synchronizing effect for ethanol (p < 0.05, Kolmogorov–Smirnov test). Conclusion Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam induces cortical network inhibition and increased synchronicity via gamma subunit containing GABAA receptors. Ethanol also induces cortical network inhibition, but without an increase in synchronicity via a wider span of molecular targets.

An electrophysiological study of single somatosensory neurons in rat granular cortex serving the limbs: a laminar analysis

1988 ◽  
Vol 60 (2) ◽  
pp. 703-724 ◽  
Author(s):  
R. W. Dykes ◽  
Y. Lamour
Keyword(s):  
Action Potential ◽  
Spontaneous Activity ◽  
Pyramidal Tract ◽  
Electrophysiological Study ◽  
Receptive Fields ◽  
Discharge Frequency ◽  
Spontaneous Discharge ◽  
Sprague Dawley ◽  
Potential Shape ◽  
Pyramidal Tract Neurons

1. Recordings were made from 545 neurons in somatosensory granular cortex of anesthetized Sprague-Dawley rats. Of this sample, 32% were active spontaneously. Active neurons were not distributed uniformly throughout cortex but were most common in layer V. The highest mean spontaneous discharge frequency also was found in this layer. Cells with the lowest rates of spontaneous activity were located immediately above and below. One subset of spontaneously active neurons was characterized by an unusually high discharge frequency modulated by somatic stimulation. 2. Only 25.8% of the 534 neurons tested in granular cortex could be activated by somatic stimuli. Only 9.4% had cutaneous receptive fields, and 2.4% received deep inputs. The remainder (14.0%) were driven by higher intensity stimuli and could not be classified unequivocally as either cutaneous or deep. The 50 neurons with cutaneous receptive fields were located in the middle third of the cortex, and those with the largest receptive fields were found most superficially. Neurons driven by somatic stimuli were found most frequently in layer Vb, where 44.5% of the sample confirmed histologically to be in layer Vb could be excited. 3. The large proportion of neurons lacking demonstrable somatic inputs was attributed to the use of iontophoretically administered glutamate, which allowed the detection of many unresponsive neurons. This proportion was not reduced by the use of nitrous oxide and halothane as an anesthetic. 4. Neurons activated only by deep inputs were found on the medial and rostral edge of the hindlimb granular cortex, suggesting that deep and cutaneous inputs may be segregated in this species. 5. Electrical stimuli applied to the foot pads activated a sample of neurons differing from those driven by natural somatic stimuli in terms of depth, spontaneous activity, probability of somatic input, and probability of activation by the pyramidal tract. 6. Pyramidal tract neurons tended to be located in layer Vb, were active spontaneously, and had evidence of somatic inputs, although most required relatively intense stimuli to be excited. Other neurons activated synaptically from the pyramidal tract were located in the layers immediately above and below the pyramidal tract neurons. These cells were divided into two groups on the basis of action-potential latency, action-potential shape, and sensitivity to acetylcholine.

scholarly journals Effects of the Volatile Anesthetic Enflurane on Spontaneous Discharge Rate and GABAA-Mediated Inhibition of Purkinje Cells in Rat Cerebellar Slices

1997 ◽  
Vol 77 (5) ◽  
pp. 2525-2538 ◽  
Author(s):  
Bernd Antkowiak ◽  
Detlef Heck
Keyword(s):  
Action Potential ◽  
Purkinje Cells ◽  
Action Potentials ◽  
Discharge Rate ◽  
Volatile Anesthetic ◽  
Spontaneous Discharge ◽  
Synaptic Inhibition ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Spontaneous Action

Antkowiak, Bernd and Detlef Heck. Effects of the volatileanesthetic enflurane on spontaneous discharge rate and GABAA-mediated inhibition of Purkinje cells in rat cerebellar slices. J. Neurophysiol. 77: 2525–2538, 1997. The effects of the volatile anesthetic enflurane on the spontaneous action potential firing and on γ-aminobutyric acid-A (GABAA)-mediated synaptic inhibition of Purkinje cells were investigated in sagittal cerebellar slices. The anesthetic shifted the discharge patterns from continuous spiking toward burst firing and decreased the frequency of extracellularly recorded spontaneous action potentials in a concentration-dependent manner. Half-maximal reduction was observed at a concentration corresponding to 2 MAC (1 MAC induces general anesthesia in 50% of patients and rats). When the GABAA antagonist bicuculline was present, 2 MAC enflurane reduced action potential firing only by 13 ± 8% (mean ± SE). In further experiments, inhibitory postsynaptic currents (IPSCs) were monitored in the whole cell patch-clamp configuration from cells voltage clamped close to −80 mV. At 1 MAC, enflurane attenuated the mean amplitude of IPSCs by 54 ± 3% while simultaneously prolonging the time courses of monoexponential current decays by 413 ± 69%. These effects were similar when presynaptic action potentials were suppressed by 1 μM tetrodotoxin. At 1–2 MAC, enflurane increased GABAA-mediated inhibition of Purkinje cells by 97 ± 20% to 159 ± 38%. During current-clamp recordings, the anesthetic (2 MAC) hyperpolarized the membrane potential by 5.2 ± 1.1 mV in the absence, but only by 1.6 ± 1.2 mV in the presence, of bicuculline. These results suggest that enflurane-induced membrane hyperpolarizations, as well as the reduction of spike rates, were partly caused by an increase in synaptic inhibition. Induction of burst firing was related to other actions of the anesthetic, probably an accelerated activation of an inwardly directed cationic current and a depression of spike afterhyperpolarizations.

scholarly journals Diazepam and ethanol differently modulate neuronal activity in organotypic cortical cultures

2019 ◽  
Author(s):  
Matthias Kreuzer ◽  
Paul S García ◽  
Verena Brucklacher-Waldert ◽  
Rebecca Claasen ◽  
Gerhard Schneider ◽  
...  
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Spectral Power ◽  
Spectral Composition ◽  
Field Potential ◽  
Cortical Network ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Action Potential Firing ◽  
Experimental Conditions

Abstract Background: The pharmacodynamic results of diazepam and ethanol administration are similar, in that each can mediate amnestic, sedative-hypnotic effects. Although each of these molecules effectively reduces the activity of central neurons, diazepam does so through modulation of a more specific set of receptor targets (GABAA receptors containing a γ-subunit), while alcohol is less selective in its receptor bioactivity. Our investigation focuses on divergent actions of diazepam and ethanol on the firing patterns of cultured cortical neurons. Method: We used electrophysiological recordings from organotypic slice cultures derived from Sprague-Dawley rat neocortex. We exposed these cultures to either diazepam (15 and 30 µM) or ethanol (30 and 60 mM) and recorded the electrical activity at baseline and experimental conditions. For analysis, we extracted the episodes of spontaneous activity, i.e., cortical up-states. After separation of action potential and local field potential (LFP) activity, we looked at differences in the number of action potentials, in the spectral power of the LFP, as well as in the coupling between action potential and LFP phase. Results: While both substances seem to decrease neocortical action potential firing in a similar fashion, diazepam seems to increase the spectral power of the up-state without impacting the spectral composition, whereas ethanol does not change the spectral power but the oscillatory architecture of the up-state. Further, the action potential to LFP-phase coupling reveals a synchronizing effect of diazepam and a (rather weak) de-synchronizing effect for ethanol. Conclusion: Diazepam and ethanol, induce specific patterns of network depressant actions. Diazepam, via gamma subunit containing GABAA receptors, induces cortical network inhibition and increased synchronicity. Ethanol, via a wider span of molecular targets, also induces cortical network inhibition, but without an increase in synchronicity.

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