scholarly journals Corticotropin-releasing factor increases Purkinje neuron excitability by modulating sodium, potassium, and Ih currents

2015 ◽  
Vol 114 (6) ◽  
pp. 3339-3350 ◽  
Author(s):  
Avraham M. Libster ◽  
Ben Title ◽  
Yosef Yarom
Keyword(s):  
Firing Rate ◽  
Stress Responses ◽  
Sodium Current ◽  
Ionic Currents ◽  
Corticotropin Releasing Factor ◽  
Voltage Dependent ◽  
Biophysical Mechanism ◽  
The Central Nervous System ◽  
Firing Properties

Corticotropin-releasing factor (CRF) is a neuromodulator closely associated with stress responses. It is synthesized and released in the central nervous system by various neurons, including neurons of the inferior olive. The targets of inferior olivary neurons, the cerebellar Purkinje neurons (PNs), are endowed with CRF receptors. CRF increases the excitability of PNs in vivo, but the biophysical mechanism is not clear. Here we examine the effect of CRF on the firing properties of PNs using acute rat cerebellar slices. CRF increased the PN firing rate, regardless of whether they were firing tonically or switching between firing and quiescent periods. Current- and voltage-clamp experiments showed that the increase in firing rate was associated with a voltage shift of the activation curve of the persistent sodium current and hyperpolarizing-activated current, as well as activation of voltage-dependent potassium current. The multiple effects on various ionic currents, which are in agreement with the possibility that activation of CRF receptors triggers several intracellular pathways, are manifested as an increase excitability of PN.

Increased ACTH response to corticotropin-releasing factor in cold-adapted rats in vivo

1989 ◽  
Vol 257 (3) ◽  
pp. E336-E339 ◽  
Author(s):  
A. Uehara ◽  
Y. Habara ◽  
A. Kuroshima ◽  
C. Sekiya ◽  
Y. Takasugi ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cold Adaptation ◽  
Corticotropin Releasing Factor ◽  
Plasma Acth ◽  
Cold Adapted ◽  
Repeated Restraint Stress ◽  
Cross Adaptation ◽  
Freely Moving ◽  
Increased Activity

We have recently reported that chronically repeated restraint stress results in improved cold tolerance in rats via an increased activity of nonshivering thermogenesis, a characteristic metabolic change observed during cold adaptation, suggesting the presence of cross-adaptation between cold and stress. It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is activated in various stress responses. In the present study, therefore, we examined whether cold adaptation would alter the adrenocorticotropic hormone (ACTH)-releasing state in vivo using freely moving, conscious rats chronically implanted with intra-atrial cannulas. There was no difference in the basal levels of plasma ACTH between warm control and cold-adapted rats. On the other hand, the ACTH response to the intravenous administration of corticotropin-releasing factor (CRF; 2 micrograms/animal) was significantly elevated in cold-adapted rats. However, the injection of 10 micrograms of CRF, which was considered as a dose to elicit the maximal ACTH response, resulted in similar ACTH release patterns between the two groups. These changes in the responsiveness of ACTH secretion have been observed in rats chronically exposed to stressful conditions. The results demonstrated in the present study, therefore, provide further evidence for our hypothesis that there may exist cross-adaptation between cold and nonthermal stress.

scholarly journals In vivo development of voltage-dependent ionic currents in embryonic Xenopus spinal neurons

1993 ◽  
Vol 13 (6) ◽  
pp. 2575-2581 ◽  
Author(s):  
MG Desarmenien ◽  
B Clendening ◽  
NC Spitzer
Keyword(s):  
Ionic Currents ◽  
Spinal Neurons ◽  
Voltage Dependent

Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells

2002 ◽  
Vol 283 (1) ◽  
pp. R115-R129 ◽  
Author(s):  
Fang-Li Zhao ◽  
Shao-Gang Lu ◽  
Scott Herness
Keyword(s):  
Intracellular Calcium ◽  
Imaging Techniques ◽  
Sodium Current ◽  
Taste Receptor ◽  
Input Resistance ◽  
Ionic Currents ◽  
Receptor Cells ◽  
Voltage Dependent ◽  
Transduction Mechanisms ◽  
Taste Receptor Cells

Although the numerous stimuli representing the taste quality of bitterness are known to be transduced through multiple mechanisms, recent studies have suggested an unpredicted complexity of the transduction pathways for individual bitter stimuli. To investigate this notion more thoroughly, a single prototypic bitter stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging techniques on dissociated rat taste receptor cells. At behaviorally relevant concentrations, caffeine produced strong inhibition of outwardly and inwardly rectifying potassium currents. Caffeine additionally inhibited calcium current, produced a weaker inhibition of sodium current, and was without effect on chloride current. Consistent with its effects on voltage-dependent currents, caffeine caused a broadening of the action potential and an increase of the input resistance. Caffeine was an effective stimulus for elevation of intracellular calcium. This elevation was concentration dependent, independent of extracellular calcium or ryanodine, and dependent on intracellular stores as evidenced by thapsigargin treatment. These dual actions on voltage-activated ionic currents and intracellular calcium levels suggest that a single taste stimulus, caffeine, utilizes multiple transduction mechanisms.

PROPERTIES OF 185TAGE-ACTIVATED IONIC CURRENTS IN CELLS FROM THE BRAINS OF THE TRICLAD FLATWORM BDELLOURA CANDIDA

1993 ◽  
Vol 185 (1) ◽  
pp. 267-286
Author(s):  
K. L. Blair ◽  
P. A. V. Anderson
Keyword(s):  
Cultured Cells ◽  
Sodium Current ◽  
Cell Voltage ◽  
Ionic Currents ◽  
Sodium Currents ◽  
Channel Evolution ◽  
Major Stage ◽  
Fast Transient ◽  
State Component

Cells were dispersed from the brains of the triclad flatworm Bdelloura candida and maintained in primary culture for up to 2 weeks. Cultured cells assumed a variety of morphologies consistent with those of neurones in vivo. Whole-cell voltage-clamp recordings from cultured cells revealed that these cells possess a variety of ionic currents, including a fast transient sodium current, a calcium current and several potassium currents. The sodium current does not inactivate completely but instead decays to a steady-state component which has the same physiology and pharmacology as the fast transient component, suggesting that the two components are carried by the same population of channels. The physiology and pharmacology of these various currents were not remarkable save for the fact that, contrary to earlier reports, all sodium currents examined were sensitive to tetrodotoxin (TTX). These animals are, therefore, the lowest animals known to possess TTX-sensitive sodium currents and, as such, represent a major stage in sodium channel evolution.

Physiologically silent sodium channels in mammalian outer hair cells

1994 ◽  
Vol 72 (2) ◽  
pp. 1037-1040 ◽  
Author(s):  
C. M. Witt ◽  
H. Y. Hu ◽  
W. E. Brownell ◽  
D. Bertrand
Keyword(s):  
Sodium Channels ◽  
Hair Cells ◽  
Sodium Current ◽  
High Sensitivity ◽  
Outer Hair Cells ◽  
Inward Current ◽  
Cell Recording ◽  
Voltage Dependent

1. Voltage-dependent properties of isolated guinea pig outer hair cells (OHCs) were investigated using whole-cell recording. An inward current was detected in approximately 10% of the cells. This inward current was identified as belonging to the voltage-activated sodium current family on the basis of its high sensitivity to tetrodotoxin and the effect of substitution of impermeant ions. Although this is the first report of a sodium current in the mammalian cochlea, it differs from the classical neuronal sodium current by having a variable magnitude from cell to cell and an inactivation that is shifted to hyperpolarized potentials. The sensory processing role of hair cells in general and outer hair cells in particular could be disrupted by the presence of a regenerative voltage-dependent current. The functional role of the OHC sodium channels is puzzling, particularly as they may be silent in vivo.

scholarly journals Transcriptome Signature of Virulent and Attenuated Pseudorabies Virus-Infected Rodent Brain

2006 ◽  
Vol 80 (4) ◽  
pp. 1773-1786 ◽  
Author(s):  
Christina Paulus ◽  
Patricia J. Sollars ◽  
Gary E. Pickard ◽  
Lynn W. Enquist
Keyword(s):  
Nervous System ◽  
Stress Responses ◽  
Pseudorabies Virus ◽  
Large Fraction ◽  
Transcriptional Response ◽  
Cellular Genes ◽  
Natural Hosts ◽  
Cellular Stress Responses ◽  
The Central Nervous System

ABSTRACT Mammalian alphaherpesviruses normally establish latent infections in ganglia of the peripheral nervous system in their natural hosts. Occasionally, however, these viruses spread to the central nervous system (CNS), where they cause damaging, often fatal, infections. Attenuated alphaherpesvirus derivatives have been used extensively as neuronal circuit tracers in a variety of animal models. Their circuit-specific spread provides a unique paradigm to study the local and global CNS response to infection. Thus, we systematically analyzed the host gene expression profile after acute pseudorabies virus (PRV) infection of the CNS using Affymetrix GeneChip technology. Rats were injected intraocularly with one of three selected virulent and attenuated PRV strains. Relative levels of cellular transcripts were quantified from hypothalamic and cerebellar tissues at various times postinfection. The number of cellular genes responding to infection correlated with the extent of virus dissemination and relative virulence of the PRV strains. A total of 245 out of 8,799 probe sets, corresponding to 182 unique cellular genes, displayed increased expression ranging from 2- to more than 100-fold higher than in uninfected tissue. Over 60% thereof were categorized as immune, proinflammatory, and other cellular defense genes. Additionally, a large fraction of infection-induced transcripts represented cellular stress responses, including glucocorticoid- and redox-related pathways. This is the first comprehensive in vivo analysis of the global transcriptional response of the mammalian CNS to acute alphaherpesvirus infection. The differentially regulated genes reported here are likely to include potential diagnostic and therapeutic targets for viral encephalitides and other neurodegenerative or neuroinflammatory diseases.

scholarly journals Effectiveness in the Block by Honokiol, a Dimerized Allylphenol from Magnolia Officinalis, of Hyperpolarization-Activated Cation Current and Delayed-Rectifier K+ Current

2020 ◽  
Vol 21 (12) ◽  
pp. 4260
Author(s):  
Ming-Huan Chan ◽  
Hwei-Hsien Chen ◽  
Yi-Ching Lo ◽  
Sheng-Nan Wu
Keyword(s):  
Surface Membrane ◽  
Ionic Currents ◽  
Gh3 Cells ◽  
Delayed Rectifier ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Voltage Dependent ◽  
K Current ◽  
Magnolia Officinalis

Background: Honokiol (HNK), a dimer of allylphenol obtained from the bark of Magnolia officinalis was demonstrated to exert an array of biological actions in different excitable cell types. However, whether or how this compound can lead to any perturbations on surface–membrane ionic currents remains largely unknown. Methods: We used the patch clamp method and found that addition of HNK effectively depressed the density of macroscopic hyperpolarization-activated cation currents (Ih) in pituitary GH3 cells in a concentration-, time- and voltage-dependent manner. By the use of a two-step voltage protocol, the presence of HNK (10 μM) shifted the steady-state activation curve of Ih density along the voltage axis to a more negative potential by approximately 11 mV, together with no noteworthy modification in the gating charge of the current. Results: The voltage-dependent hysteresis of Ih density elicited by long-lasting triangular ramp pulse was attenuated by the presence of HNK. The HNK addition also diminished the magnitude of deactivating Ih density elicited by ramp-up depolarization with varying durations. The effective half-maximal concentration (IC50) value needed to inhibit the density of Ih or delayed rectifier K+ current identified in GH3 cells was estimated to be 2.1 or 6.8 μM, respectively. In cell-attached current recordings, HNK decreased the frequency of spontaneous action currents. In Rolf B1.T olfactory sensory neurons, HNK was also observed to decrease Ih density in a concentration-dependent manner. Conclusions: The present study highlights the evidence revealing that HNK has the propensity to perturb these ionic currents and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is proposed to be a potential target for the in vivo actions of HNK and its structurally similar compounds.

Ionic currents in vertebrate myelinated nerve at hyperbaric pressure

1984 ◽  
Vol 246 (1) ◽  
pp. C84-C90 ◽  
Author(s):  
J. J. Kendig
Keyword(s):  
Steady State ◽  
Sodium Current ◽  
Ionic Currents ◽  
Base Line ◽  
Myelinated Nerve ◽  
Hyperbaric Pressure ◽  
Voltage Curve ◽  
Current Voltage ◽  
Voltage Dependent ◽  
Steady State Inactivation

To establish a base line for a study of anesthetic-pressure antagonism in axons, voltage-clamped nodes of Ranvier from amphibian sciatic nerve were subjected to pressures of 1-100 atm. Over the time of compression, there was usually an irreversible decrease in peak inward sodium current, but there was no change in peak outward sodium current or in the current-voltage relationship. The steady-state inactivation-voltage curve was shifted 5-15 mV in the depolarizing direction at 70-100 atm. The rate of rise of the sodium current was slowed, as was the time constant of inactivation (tau h). Increase in tau h was markedly voltage dependent, suggesting a selective effect of pressure on beta h, the rate constant governing development of the inactive state. The rate of development of steady-state outward potassium current was also decreased, without significant change in maximum current. The effects of pressure are qualitatively similar to, but different in detail from, those reported in squid axon and different in some details from the effects of cooling in this preparation. None of the effects can presently be related to the high-pressure nervous syndrome.

Developmental, Molecular, and Genetic Dissection of INa In Vivo in Embryonic Zebrafish Sensory Neurons

2005 ◽  
Vol 93 (6) ◽  
pp. 3582-3593 ◽  
Author(s):  
Ricardo H. Pineda ◽  
Ryan A. Heiser ◽  
Angeles B. Ribera
Keyword(s):  
Functional Properties ◽  
Developmental Stages ◽  
Sodium Current ◽  
Molecular Genetic ◽  
Genetic Dissection ◽  
Developmentally Regulated ◽  
Cell Stage ◽  
Voltage Dependent ◽  
Developing Neurons

The presence of multiple Nav1 isotypes within a neuron and the lack of specific blockers hamper identification of the in vivo roles of sodium current ( INa) components, especially during embryonic stages. To identify the functional properties of INa components in vivo in developing neurons, we took a molecular genetic approach. Embryonic zebrafish Rohon–Beard (RB) mechanosensory neurons express two different sodium channel isotypes: Nav1.1 and Nav1.6. To examine the properties of Nav1.1- and Nav1.6-encoded currents in RB cells at different developmental stages, we eliminated the contribution of Nav1.6 and Nav1.1 channels, respectively, using an antisense morpholino (MO) approach. MOs were injected into one-cell stage embryos, and RB sodium currents were recorded using patch-clamp techniques in both conventional whole cell mode as well from nucleated patches. Only a subset of RB cells appeared to be affected by the Nav1.1MO. Overall, the effect of the Nav1.1MO was a small 25% average reduction in current amplitude. Further, Nav1.1MO effects were most pronounced in RB cells of younger embryos. In contrast, the effects of the Nav1.6 MO were observed in all cells and increased as development proceeded. These results indicated that developmental upregulation of RB INa entailed an increase in the number of functional Nav1.6 channels. In addition, analysis of voltage-dependent steady-state activation and inactivation parameters revealed that specific functional properties of channels were also developmentally regulated. Finally, analysis of macho mutants indicated that developmental upregulation of INa was absent in RB cells. These results indicate that MOs are a useful tool for the molecular dissection and analysis of ion channel function in vivo.

scholarly journals Ionic currents in two strains of rat anterior pituitary tumor cells.

1984 ◽  
Vol 83 (3) ◽  
pp. 309-339 ◽  
Author(s):  
J M Dubinsky ◽  
G S Oxford
Keyword(s):  
Rate Constant ◽  
Pituitary Tumor ◽  
Calcium Current ◽  
Potassium Current ◽  
Sodium Current ◽  
Outward Current ◽  
Potassium Currents ◽  
Ionic Currents ◽  
Calcium Currents ◽  
Voltage Dependent

The ionic conductance mechanisms underlying action potential behavior in GH3 and GH4/C1 rat pituitary tumor cell lines were identified and characterized using a patch electrode voltage-clamp technique. Voltage-dependent sodium, calcium, and potassium currents and calcium-activated potassium currents were present in the GH3 cells. GH4/C1 cells possess much less sodium current, less voltage-dependent potassium current, and comparable amounts of calcium current. Voltage-dependent inward sodium current activated and inactivated rapidly and was blocked by tetrodotoxin. A slower-activating voltage-dependent inward calcium current was blocked by cobalt, manganese, nickel, zinc, or cadmium. Barium was substituted for calcium as the inward current carrier. Calcium tail currents decay with two exponential components. The rate constant for the slower component is voltage dependent, while the faster rate constant is independent of voltage. An analysis of tail current envelopes under conditions of controlled ionic gradients suggests that much of the apparent decline of calcium currents arises from an opposing outward current of low cationic selectivity. Voltage-dependent outward potassium current activated rapidly and inactivated slowly. A second outward current, the calcium-activated potassium current, activated slowly and did not appear to reach steady state with 185-ms voltage pulses. This slowly activating outward current is sensitive to external cobalt and cadmium and to the internal concentration of calcium. Tetraethylammonium and 4-aminopyridine block the majority of these outward currents. Our studies reveal a variety of macroscopic ionic currents that could play a role in the initiation and short-term maintenance of hormone secretion, but suggest that sodium channels probably do not make a major contribution.

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