scholarly journals Potassium Current Is Not Affected by Long-Term Exposure to Ghrelin or GHRP-6 in Somatotropes GC Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Belisario Domínguez Mancera ◽  
Eduardo Monjaraz Guzman ◽  
Jorge L. V. Flores-Hernández ◽  
Manuel Barrientos Morales ◽  
José M. Martínez Hernandez ◽  
...  
Keyword(s):  
Potassium Current ◽  
Functional Expression ◽  
Delayed Rectifier ◽  
Gh Secretion ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Ghs Receptor ◽  
Transitory Component

Ghrelin is a growth hormone (GH) secretagogue (GHS) and GHRP-6 is a synthetic peptide analogue; both act through the GHS receptor. GH secretion depends directly on the intracellular concentration of Ca2+; this is determined from the intracellular reserves and by the entrance of Ca2+ through the voltage-dependent calcium channels, which are activated by the membrane depolarization. Membrane potential is mainly determined by K+ channels. In the present work, we investigated the effect of ghrelin (10 nM) or GHRP-6 (100 nM) for 96 h on functional expression of voltage-dependent K+ channels in rat somatotropes: GC cell line. Physiological patch-clamp whole-cell recording was used to register the K+ currents. With Cd2+ (1 mM) and tetrodotoxin (1 μm) in the bath solution recording, three types of currents were characterized on the basis of their biophysical and pharmacological properties. GC cells showed a K+ current with a transitory component sensitive to 4-aminopyridine, which represents ~40% of the total outgoing current; a sustained component named delayed rectifier , sensitive to tetraethylammonium; and a third type of K+ current was recorded at potentials more negative than −80 mV, permitting the entrance of K+ named inward rectifier (KIR). Chronic treatment with ghrelin or GHRP-6 did not modify the functional expression of K+ channels, without significant changes () in the amplitudes of the three currents observed; in addition, there were no modifications in their biophysical properties and kinetic activation or inactivation.

Differential Oxidative Modulation of Voltage-Dependent K+ Currents in Rat Hippocampal Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2990-2995 ◽  
Author(s):  
Wolfgang Müller ◽  
Katrin Bittner
Keyword(s):  
Hydrogen Peroxide ◽  
Hippocampal Neurons ◽  
Immune Defense ◽  
Delayed Rectifier ◽  
Delayed Rectifier Current ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
K Currents ◽  
Stimulation Of

Oxidative stress is enhanced by [Ca2+]i-dependent stimulation of phospholipases and mitochondria and has been implicated in immune defense, ischemia, and excitotoxicity. Using whole cell recording from hippocampal neurons, we show that arachidonic acid (AA) and hydrogen peroxide (H2O2) both reduce the transient K+ current I A by −54 and −68%, respectively, and shift steady-state inactivation by −10 and −15 mV, respectively. While AA was effective at an extracellular concentration of 1 μM and an intracellular concentration of 1 pM, extracellular H2O2 was equally effective only at a concentration >800 μM (0.0027%). In contrast to AA, H2O2 decreased the slope of activation and increased the slope of inactivation of I A and reduced the sustained delayed rectifier current I K(V) by 22% and shifted its activation by −9 mV. Intracellular application of the antioxidant glutathione (GSH, 2–5 mM) blocked all effects of AA and the reduction of I A by H2O2. In contrast, intracellular GSH enhanced reduction of I K(V) by H2O2. Decrease of the slope of activation and increase of the slope of inactivation of I A by hydrogen peroxide was blocked and reversed to a decrease, respectively, by intracellular application of GSH. Intracellular GSH did not prevent H2O2 to shift inactivation and activation of I A and activation of I K(V) to more negative potentials. We conclude, that AA and H2O2modulate voltage-activated K currents differentially by oxidation of GSH accessible intracellular and GSH inaccessible extracellular K+-channel domains, thereby presumably affecting neuronal information processing and oxidative damage.

Two temporally overlapping "delayed-rectifiers" determine the voltage-dependent potassium current phenotype in cultured hippocampal interneurons

1996 ◽  
Vol 76 (3) ◽  
pp. 1477-1490 ◽  
Author(s):  
A. Chikwendu ◽  
C. J. McBain
Keyword(s):  
Potassium Current ◽  
Critical Role ◽  
Relative Proportion ◽  
Minor Component ◽  
Transient Current ◽  
Stratum Radiatum ◽  
Delayed Rectifier ◽  
Gamma Aminobutyric Acid ◽  
Current Component ◽  
Voltage Dependent

1. Whole cell voltage-clamp recordings were used to characterize the calcium-independent "delayed-rectifier" potassium currents of gamma-aminobutyric acid (GABA)-positive stratum radiatum-lacunosum-moleculare (st. L-M) interneurons in primary culture derived from neonate rats [postnatal day 5-7 (P5-P7)]. 2. Two distinct current phenotypes were observed, which we termed "sustained" and "slowly inactivating." Despite possessing similar voltage-dependent activation properties, current differed in their time-dependent inactivation properties and their kinetics of activation and deactivation. The phenotypes of the observed currents did not change during the time in vitro. The total current phenotype observed in any cell likely resulted from the temporal overlap of the two current components expressed in different relative proportions. 3. Externally applied 4-aminopyridine (4-AP) selectively blocked the slowly inactivating current component, by a use-dependent, but voltage-independent mechanism, suggesting that channel activation is required for 4-AP to interact with its binding site. In contrast, the sustained current component was unaffected by 4-AP. 4. Both the slowly inactivating and sustained current phenotypes were sensitive to externally applied tetraethylammonium (TEA). The IC50 of block by TEA was lower in cells expressing predominantly the sustained current components. 5. Currents recorded in the presence of internally applied TEA were of a slowly inactivating phenotype, suggesting that [TEA]i preferentially blocked the sustained current component. 6. When test pulses were preceded by a prepulse to -100 mV, a transient A-type current component was observed, but in contrast to pyramidal neurons and other interneuron types, this transient current contributed only a minor component to the total initial peak current. 7. In conclusion, two distinct, temporally overlapping potassium current phenotypes were observed on st. L-M interneurons. The overall phenotype was determined by the relative proportion of each current component. The absence of a prominent transient current suggests that the two delayed-rectifier currents play a critical role in determining the firing characteristics of these interneurons.

scholarly journals Specific Involvement of Gonadal Hormones in the Functional Maturation of Growth Hormone Releasing Hormone (GHRH) Neurons

Endocrinology ◽  
2010 ◽  
Vol 151 (12) ◽  
pp. 5762-5774 ◽  
Author(s):  
Laurie-Anne Gouty-Colomer ◽  
Pierre-François Méry ◽  
Emilie Storme ◽  
Elodie Gavois ◽  
Iain C. Robinson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Postnatal Development ◽  
Potassium Current ◽  
Hormonal Treatment ◽  
Gonadal Hormones ◽  
Detailed Knowledge ◽  
Releasing Hormone ◽  
Electrophysiological Properties ◽  
Gh Secretion ◽  
Voltage Dependent

Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.

scholarly journals Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier K+-Channel Currents in Murine Thymocytes

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kazutomo Saito ◽  
Nozomu Abe ◽  
Hiroaki Toyama ◽  
Yutaka Ejima ◽  
Masanori Yamauchi ◽  
...  
Keyword(s):  
Plasma Membranes ◽  
Second Generation ◽  
Membrane Capacitance ◽  
K Channel ◽  
Delayed Rectifier ◽  
Cell Recording ◽  
Voltage Dependent ◽  
Proliferation Of Lymphocytes ◽  
First Time ◽  
Channel Currents

Background/Aims. Voltage-dependent potassium channels (Kv1.3) are predominantly expressed in lymphocyte plasma membranes. These channels are critical for the activation and proliferation of lymphocytes. Since second-generation antihistamines are lipophilic and exert immunomodulatory effects, they are thought to affect the lymphocyte Kv1.3-channel currents. Methods. Using the patch-clamp whole-cell recording technique in murine thymocytes, we tested the effects of second-generation antihistamines, such as cetirizine, fexofenadine, azelastine, and terfenadine, on the channel currents and the membrane capacitance. Results. These drugs suppressed the peak and the pulse-end currents of the channels, although the effects of azelastine and terfenadine on the peak currents were more marked than those of cetirizine and fexofenadine. Both azelastine and terfenadine significantly lowered the membrane capacitance. Since these drugs did not affect the process of endocytosis in lymphocytes, they were thought to have interacted directly with the plasma membranes. Conclusions. Our study revealed for the first time that second-generation antihistamines, including cetirizine, fexofenadine, azelastine, and terfenadine, exert suppressive effects on lymphocyte Kv1.3-channels. The efficacy of these drugs may be related to their immunomodulatory mechanisms that reduce the synthesis of inflammatory cytokine.

Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina

1992 ◽  
Vol 68 (4) ◽  
pp. 1143-1150 ◽  
Author(s):  
Y. Ueda ◽  
A. Kaneko ◽  
M. Kaneda
Keyword(s):  
Potassium Current ◽  
Horizontal Cell ◽  
Potassium Currents ◽  
Ionic Currents ◽  
Horizontal Cells ◽  
Membrane Properties ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Cat Retina ◽  
Voltage Dependent

1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Up-regulation of L-type Voltage-dependent Calcium Channels after Long Term Exposure to Nicotine in Cerebral Cortical Neurons

2001 ◽  
Vol 277 (10) ◽  
pp. 7979-7988 ◽  
Author(s):  
Masashi Katsura ◽  
Yutaka Mohri ◽  
Keijiro Shuto ◽  
Yan Hai-Du ◽  
Taku Amano ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Cortical Neurons ◽  
Cerebral Cortical Neurons ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

scholarly journals REST levels affect the functional expression of voltage dependent calcium channels and the migratory activity in immortalized GnRH neurons

2016 ◽  
Vol 629 ◽  
pp. 19-25
Author(s):  
Susanna Antoniotti ◽  
Federico Alessandro Ruffinatti ◽  
Simona Torriano ◽  
Anna Luganini ◽  
Rosalba D’Alessandro ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Functional Expression ◽  
Migratory Activity ◽  
Gnrh Neurons ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels

Evidence for a delayed rectifier-like potassium current in the clonal rat pituitary cell line GH3

1991 ◽  
Vol 261 (1) ◽  
pp. E66-E75 ◽  
Author(s):  
S. M. Simasko
Keyword(s):  
Cell Line ◽  
Potassium Current ◽  
Slow Component ◽  
Pituitary Cell ◽  
Gh3 Cells ◽  
Delayed Rectifier ◽  
Time Constants ◽  
Calcium Dependent ◽  
Rat Pituitary ◽  
Voltage Dependent

Whole cell patch-clamp techniques were used to investigate voltage-dependent potassium currents in the clonal rat pituitary cell line GH3. Inactivation of the voltage-dependent potassium current was best fit by two time constants (50–80 ms and 2–3 s) plus a sustained value. These components of inactivation could be separated based on their voltage-dependent properties and pharmacological sensitivity to 10 mM tetraethylammonium (TEA) and 5 mM 4-aminopyridine (4-AP). The fast component begins to activate around -50 mV, is half-maximally activated at -19 mV, is 50% inactivated at -55 mV, and is sensitive to 4-AP but insensitive to TEA. The slow component begins to activate at around -10 mV, is half-maximally activated at +4 mV, is 50% inactivated at -23 mV, and is sensitive to both TEA and 4-AP. The sustained component is apparent by 0 mV but has not yet reached half-maximal activation at +57 mV. It is somewhat sensitive to TEA but relatively resistant to 4-AP. In the presence of TEA it was found that the fast-inactivating component actually inactivated in a biphasic manner with time constants of approximately 50 and 500 ms. From the properties of these components it is concluded that at least three distinct voltage-dependent potassium channel types exist in GH3 cells as follows: an A-like current (fast-inactivating component), a delayed rectifier-like current (slow-inactivating component), and the voltage-dependent properties of calcium-dependent potassium channels (the sustained component).

Isolation and characterization of IKr in cardiac myocytes by Cs+ permeation

2006 ◽  
Vol 290 (3) ◽  
pp. H1038-H1049 ◽  
Author(s):  
Shetuan Zhang
Keyword(s):  
Cardiac Myocytes ◽  
Potassium Current ◽  
Ventricular Myocytes ◽  
Delayed Rectifier ◽  
Pharmacological Properties ◽  
Membrane Expression ◽  
Isolation And Characterization ◽  
Recovery From Inactivation ◽  
Voltage Dependent ◽  
Herg Current

Isolation of the rapidly activating delayed rectifier potassium current ( IKr) from other cardiac currents has been a difficult task for quantitative study of this current. The present study was designed to separate IKr using Cs+ in cardiac myocytes. Cs+ have been known to block a variety of K+ channels, including many of those involved in the cardiac action potential such as inward rectifier potassium current IK1 and the transient outward potassium current Ito. However, under isotonic Cs+ conditions (135 mM Cs+), a significant membrane current was recorded in isolated rabbit ventricular myocytes. This current displayed the voltage-dependent onset of and recovery from inactivation that are characteristic to IKr. Consistently, the current was selectively inhibited by the specific IKr blockers. The biophysical and pharmacological properties of the Cs+-carried human ether-a-go-go-related gene (hERG) current were very similar to those of the Cs+-carried IKr in ventricular myocytes. The primary sequence of the selectivity filter in hERG was in part responsible for the Cs+ permeability, which was lost when the sequence was changed from GFG to GYG, characteristic of other, Cs+-impermeable K+ channels. Thus the unique high Cs+ permeability in IKr channels provides an effective way to isolate IKr current. Although the biophysical and pharmacological properties of the Cs+-carried IKr are different from those of the K+-carried IKr, such an assay enables IKr current to be recorded at a level that is large enough and sufficiently robust to evaluate any IKr alterations in native tissues in response to physiological or pathological changes. It is particularly useful for exploring the role of reduction of IKr in arrhythmias associated with heart failure and long QT syndrome due to the reduced hERG channel membrane expression.

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