scholarly journals Serotonin regulates voltage-dependent currents in type Ie(A) and Ii interneurons of Hermissenda

2011 ◽  
Vol 106 (5) ◽  
pp. 2557-2569 ◽  
Author(s):  
Nan Ge Jin ◽  
Terry Crow
Keyword(s):  
Nervous System ◽  
Intrinsic Excitability ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Type I ◽  
Activation Curve ◽  
Inactivation Curve ◽  
Whole Cell ◽  
Different Types ◽  
Hyperpolarizing Shift

Serotonin (5-HT) has both direct and modulatory actions on central neurons contributing to behavioral arousal and cellular-synaptic plasticity in diverse species. In Hermissenda, 5-HT produces changes in intrinsic excitability of different types of identified interneurons in the circumesophageal nervous system. Using whole cell patch-clamp techniques we have examined membrane conductance changes produced by 5-HT that contribute to intrinsic excitability in two identified classes of interneurons, types Ii and IeA. Whole cell currents were examined before and after 5-HT application to the isolated nervous system. A 4-aminopyridine-sensitive transient outward K+ current [ IK(A)], a tetraethylammonium-sensitive delayed rectifier K+ current [ IK(V)], an inward rectifier K+ current [ IK(IR)], and a hyperpolarization-activated current ( Ih) were characterized. 5-HT decreased the amplitude of IK(A) and IK(V) in both type Ii and IeA interneurons. However, differences in 5-HT's effects on the activation-inactivation kinetics were observed in different types of interneurons. 5-HT produced a depolarizing shift in the activation curve of IK(V) and a hyperpolarizing shift in the inactivation curve of IK(A) in type Ii interneurons. In contrast, 5-HT produced a depolarizing shift in the activation curve and a hyperpolarizing shift in the inactivation curve of both IK(V) and IK(A) in type IeA interneurons. In addition, 5-HT decreased the amplitude of IK(IR) in type Ii interneurons and increased the amplitude of Ih in type IeA interneurons. These results indicate that 5-HT-dependent changes in IK(A), IK(V), IK(IR), and Ih contribute to multiple mechanisms that synergistically support modulation of increased intrinsic excitability associated with different functional classes of identified type I interneurons.

Potassium currents in mammalian and avian isolated type I semicircular canal hair cells

1994 ◽  
Vol 71 (1) ◽  
pp. 317-329 ◽  
Author(s):  
K. J. Rennie ◽  
M. J. Correia
Keyword(s):  
Membrane Potential ◽  
Hair Cells ◽  
Potassium Current ◽  
Columba Livia ◽  
Membrane Properties ◽  
Delayed Rectifier ◽  
Type I ◽  
Type Ii ◽  
Current Clamp ◽  
Whole Cell

1. Type I vestibular hair cells were isolated from the cristae ampullares of the semicircular canals of the Mongolian gerbil (Meriones unguiculatus) and the white king pigeon (Columba livia). Dissociated type I cells were distinguished from type II hair cells by their neck to plate ratio (NPR) and their characteristic amphora shape. 2. The membrane properties of gerbil and pigeon type I hair cells were studied in whole-cell voltage- and current-clamp using the perforated patch technique with amphotericin B as the perforating agent. 3. In whole-cell current-clamp, the average zero-current potential, Vz, measured for pigeon type I hair cells, was -70 +/- 7 (SD) mV (n = 18) and -71 +/- 11 mV (n = 83) for gerbil type I hair cells. 4. At Vz, for both gerbil and pigeon type I hair cells, a potassium current (IKI) was > or = 50% activated. This current deactivated rapidly when the membrane potential was hyperpolarized below -90 mV. 5. IKI was blocked by externally applied 4-aminopyridine (4-AP) (5 mM) and by internally applied 20 mM tetraethylammonium (TEA). It was also reduced when 4 mM barium was present in the external solution. The degree of block by barium increased as the membrane potential became more positive. External cesium (5 mM) blocked the inward component of IKI. When IKI was pharmacologically blocked, Vz depolarized by approximately 40 mV. Therefore IKI appears to be a delayed rectifier and to set the more negative Vz noted for isolated type I hair cells when compared to isolated type II hair cells, which do not have IKI. 6. A second, smaller potassium current was present at membrane potential depolarizations above -40 mV. This current was blocked by 30-50 mM, externally applied TEA, 100 microM quinidine, 100 nM apamin, but not 100 nM charybdotoxin, indicating that this is a calcium-activated potassium current, IK(Ca), different from the maxi-K calcium-activated potassium current found in most other hair cells.

scholarly journals Bursting in cerebellar stellate cells induced by pharmacological agents: Non-sequential spike adding

2020 ◽  
Vol 16 (12) ◽  
pp. e1008463
Author(s):  
Saeed Farjami ◽  
Ryan P. D. Alexander ◽  
Derek Bowie ◽  
Anmar Khadra
Keyword(s):  
Stellate Cells ◽  
Delayed Rectifier ◽  
Type Model ◽  
Type I ◽  
Low Doses ◽  
Pharmacological Agents ◽  
Whole Cell ◽  
Square Wave ◽  
Cell Configuration ◽  
High Doses

Cerebellar stellate cells (CSCs) are spontaneously active, tonically firing (5-30 Hz), inhibitory interneurons that synapse onto Purkinje cells. We previously analyzed the excitability properties of CSCs, focusing on four key features: type I excitability, non-monotonic first-spike latency, switching in responsiveness and runup (i.e., temporal increase in excitability during whole-cell configuration). In this study, we extend this analysis by using whole-cell configuration to show that these neurons can also burst when treated with certain pharmacological agents separately or jointly. Indeed, treatment with 4-Aminopyridine (4-AP), a partial blocker of delayed rectifier and A-type K+ channels, at low doses induces a bursting profile in CSCs significantly different than that produced at high doses or when it is applied at low doses but with cadmium (Cd2+), a blocker of high voltage-activated (HVA) Ca2+ channels. By expanding a previously revised Hodgkin–Huxley type model, through the inclusion of Ca2+-activated K+ (K(Ca)) and HVA currents, we explain how these bursts are generated and what their underlying dynamics are. Specifically, we demonstrate that the expanded model preserves the four excitability features of CSCs, as well as captures their bursting patterns induced by 4-AP and Cd2+. Model investigation reveals that 4-AP is potentiating HVA, inducing square-wave bursting at low doses and pseudo-plateau bursting at high doses, whereas Cd2+ is potentiating K(Ca), inducing pseudo-plateau bursting when applied in combination with low doses of 4-AP. Using bifurcation analysis, we show that spike adding in square-wave bursts is non-sequential when gradually changing HVA and K(Ca) maximum conductances, delayed Hopf is responsible for generating the plateau segment within the active phase of pseudo-plateau bursts, and bursting can become “chaotic” when HVA and K(Ca) maximum conductances are made low and high, respectively. These results highlight the secondary effects of the drugs applied and suggest that CSCs have all the ingredients needed for bursting.

scholarly journals Actions of FTY720 (Fingolimod), a Sphingosine-1-Phosphate Receptor Modulator, on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-Lymphocytes

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4525
Author(s):  
Wei-Ting Chang ◽  
Ping-Yen Liu ◽  
Sheng-Nan Wu
Keyword(s):  
T Lymphocytes ◽  
Immune Cells ◽  
K Channel ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Dependent Manner ◽  
Inactivation Curve ◽  
K Channels ◽  
Sphingosine 1 Phosphate ◽  
K Current

FTY720 (fingolimod), a modulator of sphingosine-1-phosphate receptors, is known to produce the immunomodulatory actions and to be beneficial for treating the relapsing multiple sclerosis. However, whether it exerts any effects on membrane ion currents in immune cells remains largely unknown. Herein, the effects of FTY720 on ionic currents in Jurkat T-lymphocytes were investigated. Cell exposure to FTY720 suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in a time- and concentration-dependent manner with an IC50 value of 1.51 μM. Increasing the FTY720 concentration not only decreased the IK(DR) amplitude but also accelerated the inactivation time course of the current. By using the minimal reaction scheme, the effect of FTY720 on IK(DR) inactivation was estimated with a dissociation constant of 3.14 μM. FTY720 also shifted the inactivation curve of IK(DR) to a hyperpolarized potential with no change in the slope factor, and recovery from IK(DR) became slow during the exposure to this compound. Cumulative inactivation for IK(DR) in response to repetitive depolarizations was enhanced in the presence of FTY720. In SEW2871-treated cells, FTY720-induced inhibition of IK(DR) was attenuated. This compound also exerted a stimulatory action on the activity of intermediate-conductance Ca2+-activated K+ channels in Jurkat T-lymphocytes. However, in NSC-34 neuronal cells, FTY720 did not modify the inactivation kinetics of KV3.1-encoded IK(DR), although it suppressed IK(DR) amplitude in these cells. Collectively, the perturbations by FTY720 on different types of K+ channels may contribute to the functional activities of immune cells, if similar findings appear in vivo.

Voltage-Dependent Sodium and Calcium Currents in Acutely Isolated Adult Rat Trigeminal Root Ganglion Neurons

1999 ◽  
Vol 81 (3) ◽  
pp. 1123-1134 ◽  
Author(s):  
Hyung-Chan Kim ◽  
Man-Kyo Chung
Keyword(s):  
Calcium Currents ◽  
Inactivation Kinetics ◽  
Type I ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Adult Rat ◽  
Voltage Dependent ◽  
Trigeminal Root ◽  
Ganglion Neurons ◽  
Drug Free

Voltage-dependent sodium and calcium currents in acutely isolated adult rat trigeminal root ganglion neurons. Voltage-dependent sodium ( I Na) and calcium ( I Ca) currents in small (<30 μM) neurons from adult rat trigeminal root ganglia were characterized with a standard whole cell patch-clamp technique. Two types of I Na showing different sensitivity to tetrodotoxin (TTX) were recorded, which showed marked differences in their activating and inactivating time courses. The activation and the steady-state inactivation kinetics of TTX-resistant I Na were more depolarized by about +20 and +30 mV, respectively, than those of TTX-sensitive I Na. Voltage-dependent I Ca was recorded under the condition that suppressed sodium and potassium currents with 10 mM Ca2+ as a charge carrier. Depolarizing step pulses from a holding potential of −80 mV evoked two distinct inward I Ca, low-voltage activated (LVA) and high-voltage activated (HVA) I Ca. LVA I Ca was first observed at −60 to −50 mV and reached a peak at about −30 mV. Amiloride (0.5 mM) suppressed ∼60% of the LVA I Ca, whereas ∼10% of HVA I Ca was inhibited by the same concentration of the amiloride. LVA I Ca was far less affected by the presence of external Cd2+ or the replacement of Ca2+ by 10 Ba2+ than HVA I Ca. The ω-conotoxin GVIA (ω-CgTx), an N-type I Ca blocker, suppressed ∼65% of the whole cell HVA I Ca at the concentration of 1 μM. The ω-CgTx-resistant HVA I Ca was sensitive to nifedipine (10 μM), a dihydropyridine (DHP) calcium channel antagonist, which produced an additional blockade by ∼25% of the drug-free control (∼70% of the ω-CgTx-resistant I Ca). The combination of 10 μM nifedipine and 1 μM ω-CgTx left ∼13% of the drug-free control I Ca unblocked. The DHP agonist S(−)-BayK8644 (5 μM) shifted the activation of the HVA I Ca to more negative potentials and increased its maximal amplitude. Additionally, S(−)-BayK8644 caused the appearance of a slowed component of the tail current. These results clearly demonstrate that the presence of two types of sodium channels, TTX sensitive and resistant, and three types of calcium channels, T, L, and N type, in the small-sized adult rat trigeminal ganglion neurons.

Extracellular Ba2+ blocks the cardiac transient outward K+ current

2000 ◽  
Vol 278 (1) ◽  
pp. H295-H299 ◽  
Author(s):  
Hong Shi ◽  
Hui-Zhen Wang ◽  
Zhiguo Wang
Keyword(s):  
Patch Clamp ◽  
Inward Rectifier ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Atrial Myocytes ◽  
Whole Cell ◽  
Whole Cell Patch Clamp ◽  
Potent Inhibition ◽  
Voltage Dependent ◽  
K Current

Ba2+ is widely used as a tool in patch-clamp studies because of its ability to block a variety of K+channels and to pass Ca2+ channels. Its potential ability to block the cardiac transient outward K+ current ( I to) has not been clearly documented. We performed whole cell patch-clamp studies in canine ventricular and atrial myocytes. Extracellular application of Ba2+ produced potent inhibition of I to with an IC50 of ∼40 μM. The effects were voltage independent, and the inactivation kinetics were not altered by Ba2+. The potency of Ba2+ was ∼10 times higher than that of 4-aminopyridine (a selective I to blocker with an IC50 of 430 μM) under identical conditions. By comparison, Ba2+blockade of the inward rectifier K+ current was voltage dependent; the IC50 was ∼20 times lower (2.5 μM) than that for I to when determined at −100 mV and was comparable to I to as determined at −60 mV (IC50 = 26 μM). Ba2+ concentrations of ≤1 mM or higher failed to block ultrarapid delayed rectifier K+ current. Our data suggest that Ba2+ can be considered a potent blocker of I to.

Methionine-Specific Staining of Collagen

1982 ◽  
Vol 40 ◽  
pp. 294-295
Author(s):  
E.M. Kuhn ◽  
K.D. Marenus ◽  
M. Beer
Keyword(s):  
Amino Acids ◽  
Collagen Fibers ◽  
Type Iii Collagen ◽  
Type I ◽  
Electron Microscopic ◽  
Good Correspondence ◽  
Specific Staining ◽  
Type Iii ◽  
Different Types ◽  
Sulfur Containing

Fibers composed of different types of collagen cannot be differentiated by conventional electron microscopic stains. We are developing staining procedures aimed at identifying collagen fibers of different types.Pt(Gly-L-Met)Cl binds specifically to sulfur-containing amino acids. Different collagens have methionine (met) residues at somewhat different positions. A good correspondence has been reported between known met positions and Pt(GLM) bands in rat Type I SLS (collagen aggregates in which molecules lie adjacent to each other in exact register). We have confirmed this relationship in Type III collagen SLS (Fig. 1).

scholarly journals Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3028
Author(s):  
George I. Lambrou ◽  
Apostolos Zaravinos ◽  
Maria Braoudaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cns Tumors ◽  
Normal Brain ◽  
Cns Tumor ◽  
Different Types ◽  
Receiver Operator Curve Analysis ◽  
The Central Nervous System ◽  
Tumor Types ◽  
Operator Curve

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

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