scholarly journals Increased ACh-Associated Immunoreactivity in Autonomic Centers in PTZ Kindling Model of Epilepsy

Biomedicines ◽  
2020 ◽  
Vol 8 (5) ◽  
pp. 113 ◽  
Author(s):  
Enes Akyüz ◽  
Züleyha Doğanyiğit ◽  
Yam Nath Paudel ◽  
Emin Kaymak ◽  
Seher Yilmaz ◽  
...  
Keyword(s):  
Ion Channel ◽  
Resting Membrane Potential ◽  
Cardiac Pathology ◽  
Kindling Model ◽  
Cell Excitability ◽  
Ptz Kindling ◽  
Targeted Expression ◽  
Inwardly Rectifying ◽  
Histological Staining

Experimental and clinical studies of cardiac pathology associated with epilepsy have demonstrated an impact on the autonomic nervous system (ANS). However, the underlying molecular mechanism has not been fully elucidated. Molecular investigation of the neurotransmitters related receptor and ion channel directing ANS might help in understanding the associated mechanism. In this paper, we investigated the role of acetylcholine (ACh), which demonstrates both sympathetic and parasympathetic roles in targeted expression in terms of the relevant receptor and ion channel. Inwardly rectifying potassium (Kir) channels play a significant role in maintaining the resting membrane potential and controlling cell excitability and are prominently expressed in both the excitable and non-excitable tissues. The immunoreactivity of ACh-activated Kir3.1 channel and muscarinic ACh receptors (M2) in autonomic centers such as the brainstem, vagus nerve (VN) and atria of heart was confirmed by both histological staining and pathological tissue analysis. Significant upregulations of Kir3.1 and M2 receptors were observed in pentylenetetrazol (PTZ)-kindled epileptic rats for all related tissues investigated, whereas no pathological difference was observed. These findings provide proof-of-concept that changes in ACh-associated immunoreactivity might be linked to the ANS dysfunctions associated with epilepsy.

A possible role of inwardly rectifying K+ channels in chick myoblast differentiation

1997 ◽  
Vol 272 (3) ◽  
pp. C894-C900 ◽  
Author(s):  
K. S. Shin ◽  
J. Y. Park ◽  
H. Kwon ◽  
C. H. Chung ◽  
M. S. Kang
Keyword(s):  
Time Course ◽  
Developmental Change ◽  
Myoblast Differentiation ◽  
Resting Membrane Potential ◽  
K Channels ◽  
K Concentration ◽  
Inwardly Rectifying ◽  
K Permeability ◽  
K Currents

We examined the developmental change of inwardly rectifying K+ channels (IRK) and its possible role in myogenesis. Northern blot analysis revealed an increase in the level of IRK mRNA during myogenesis. Accordingly, IRK current was not detectable in replicating myoblasts but first appeared in aligned myoblasts that were competent for fusion and gradually increased thereafter. The time course change of IRK activity was closely related to the increase in resting membrane potential during myogenesis. Application of 0.5 mM Ba2+ to the bath depolarized the membrane and blocked IRK currents dramatically but not outwardly rectifying K+ currents. Myoblasts devoid of IRK had low resting K+ permeability, whereas myotubes that possess IRK had high resting K+ permeability. In some aligned myoblasts, anomalous hyperpolarization was elicited by increasing extracellular K+ concentration, which may be attributable to the increased conductance of IRK. Noteworthy was the fact that maximal fusion was obtained at this range of K+ concentration. These findings imply that IRK is responsible for the change in the K+ permeability during chick myogenesis, which may provide a larger driving force for Ca2+ influx that is a prerequisite for myoblast fusion.

scholarly journals Immunoreactivity of Muscarinic Acetylcholine M2 and Serotonin 5-HT2B Receptors, Norepinephrine Transporter and Kir Channels in a Model of Epilepsy

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 276
Author(s):  
Enes Akyuz ◽  
Zuleyha Doganyigit ◽  
Yam Nath Paudel ◽  
Betul Koklu ◽  
Emin Kaymak ◽  
...  
Keyword(s):  
K Channel ◽  
Neurotransmitter Receptors ◽  
Extracellular Potassium ◽  
Unexpected Death ◽  
Kir Channels ◽  
Ptz Kindling ◽  
Neurotransmitter Activity ◽  
K Concentration ◽  
Inwardly Rectifying

Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adult Wistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.

Effect of low chloride on relaxation in hamster diaphragm muscle

1986 ◽  
Vol 61 (1) ◽  
pp. 180-184 ◽  
Author(s):  
S. A. Esau ◽  
N. Sperelakis
Keyword(s):  
Membrane Potential ◽  
Muscle Fatigue ◽  
Time Constant ◽  
Diaphragm Muscle ◽  
Resting Membrane Potential ◽  
Krebs Solution ◽  
Sarcolemmal Membrane ◽  
Cl Conductance

With muscle fatigue the chloride (Cl-) conductance of the sarcolemmal membrane decreases. The role of lowered Cl- conductance in the prolongation of relaxation seen with fatigue was studied in isolated hamster diaphragm strips. The muscles were studied in either a Krebs solution or a low Cl- solution in which half of the NaCl was replaced by Na-gluconate. Short tetanic contractions were produced by a 160-ms train of 0.2-ms pulses at 60 Hz from which tension (T) and the time constant of relaxation were measured. Resting membrane potential (Em) was measured using KCl-filled microelectrodes with resistances of 15–20 M omega. Mild fatigue (20% fall in tension) was induced by 24–25 tetanic contractions at the rate of 2/s. There was no difference in Em or T in the two solutions, either initially or with fatigue. The time constant of relaxation was greater in low Cl- solution, both initially (22 +/- 3 vs. 18 +/- 5 ms, mean +/- SD, P less than 0.05) and with fatigue (51 +/- 18 vs. 26 +/- 7 ms, P less than 0.005). Lowering of sarcolemmal membrane Cl- conductance appears to play a role in the slowing of relaxation of hamster diaphragm muscle seen with fatigue.

scholarly journals Involvement of A pertussis Toxin Sensitive G-Protein in the Inhibition of Inwardly Rectifying K+Currents by Platelet-Activating Factor in Guinea-Pig Atrial Cardiomyocytes

1994 ◽  
Vol 3 (1) ◽  
pp. 45-51
Author(s):  
M. Gollasch ◽  
T. Kleppisch ◽  
D. Krautwurst ◽  
D. Lewinsohn ◽  
J. Hescheler
Keyword(s):  
Cyclic Amp ◽  
Guinea Pig ◽  
G Protein ◽  
Pertussis Toxin ◽  
Platelet Activating Factor ◽  
Resting Membrane Potential ◽  
Patch Clamp Technique ◽  
Guinea Pig Heart ◽  
Ventricular Cells ◽  
Inwardly Rectifying

Platelet-activating factor (PAF) inhibits single inwardly rectifying K+channels in guinea-pig ventricular cells. There is currently little information as to the mechanism by which these channels are modulated. The effect of PAF on quasi steady-state inwardly rectifying K+currents (presumably of the IK1type) of auricular, atrial and ventricular cardiomyocytes from guinea-pig were studied. Applying the patch-clamp technique in the whole-cell configuration, PAF (10 nM) reduced the K+currents in all three cell types. The inhibitory effect of PAF occurred within seconds and was reversible upon wash-out. It was almost completely abolished by the PAF receptor antagonist BN 50730. Intracellular infusion of atrial cells with guanine 5′-(β-thio)diphosphate (GDPS) or pretreatment of cells with pertussis toxin abolished the PAF dependent reduction of the currents. Neither extracellularly applied isoproterenol nor intracellularly applied adenosine 3′,5′-cyclic monophosphate (cyclic AMP) attenuated the PAF effect. In multicellular preparations of auricles, PAF (10 nM) induced arrhythmias. The arrhythmogenic activity was also reduced by BN 50730. The data indicate that activated PAF receptors inhibit inwardly rectifying K+currents via a pertussis toxin sensitive G-protein without involvement of a cyclic AMP-dependent step. Since IK1is a major component in stabilizing the resting membrane potential, the observed inhibition of this type of channel could play an important role in PAF dependent arrhythmogenesis in guinea-pig heart.

scholarly journals pH-Insensitive FRET Voltage Dyes

2007 ◽  
Vol 12 (5) ◽  
pp. 656-667 ◽  
Author(s):  
Michael P. Maher ◽  
Nyan-Tsz Wu ◽  
Hong Ao
Keyword(s):  
Ion Channel ◽  
High Throughput ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
High Sensitivity ◽  
Fast Response ◽  
Resting Membrane Potential ◽  
Absolute Calibration ◽  
High Throughput Assay ◽  
Voltage Sensitive Dyes

Many high-throughput ion channel assays require the use of voltage-sensitive dyes to detect channel activity in the presence of test compounds. Dye systems employing Förster resonance energy transfer (FRET) between 2 membrane-bound dyes are advantageous in combining high sensitivity, relatively fast response, and ratiometric output. The most widely used FRET voltage dye system employs a coumarin fluorescence donor whose excitation spectrum is pH dependent. The authors have validated a new class of voltage-sensitive FRET donors based on a pyrene moiety. These dyes are significantly brighter than CC2-DMPE and are not pH sensitive in the physiological range. With the new dye system, the authors demonstrate a new high-throughput assay for the acid-sensing ion channel (ASIC) family. They also introduce a novel method for absolute calibration of voltage-sensitive dyes, simultaneously determining the resting membrane potential of a cell. ( Journal of Biomolecular Screening 2007:656-667)

Sign in / Sign up

Export Citation Format

Share Document