جستجوی مقالات مرتبط با کلیدواژه "potassium channels" در نشریات گروه "پزشکی"

In the present study, the relaxant effect of crocetin on tracheal smooth muscle cells (TSM) and its possible mechanisms were evaluated.

The study was conducted on 54 male Wistar rats in 8 groups. TSM was contracted by methacholine (10 μM) and KCl (60 mM), and the relaxant effects of four cumulative concentrations of crocetin, petal extract of saffron, and theophylline were examined on non-incubated and TSM incubated with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide, and indomethacin were investigated. 

In non-incubated TSM contracted by methacholine or KCl, crocetin and theophylline showed concentration-dependent relaxant effects (all, P<0.001). However, various concentrations of crocetin showed significantly lower relaxant effects compared to those of theophylline (all, P<0.001). In the methacholine-induced contraction of TSM, the relaxation effect of the last concentration of crocetin in the TSM incubated with propranolol was lower than in non-incubated TSM (P<0.05). In the incubated TSM with chlorpheniramine, the relaxant effects of the two last concentrations of crocetin were significantly lower than in the non-incubated tissues contracted by KCl (P<0.05 and P<0.0). The levels of EC50 crocetin in the incubated TSM with glibenclamide, chlorpheniramine, and indomethacin were markedly lower than in non-incubated (all, P<0.05). 

The results showed potent relaxation effects of crocetin on TSM and were suggested to be through stimulation of ß-adrenergic receptors, inhibition of histamine (H1) receptors, and potassium channel opening mechanisms.

The present research aimed to identify the functional effects and underlying mechanisms of metformin on the rat thoracic aorta. Thoracic aorta segments of Wistar Albino rats were put in the chambers of an isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration time, potassium chloride or phenylephrine was used to contract the vascular segments. The vessel segments were cumulatively treated with metformin (10-7–10-3 M) when a steady contraction was achieved. The described experimental approach was repeated after incubations with signaling pathway inhibitors and selective blockers of potassium channels to identify the effect mechanisms of metformin. Metformin had a potent vasorelaxant effect in a concentration-dependent way (P<0.001). After the endothelium was removed, the vasorelaxant effect level of metformin was significantly reduced. The level of vasorelaxant effect of metformin was increased by the maintenance of perivascular adipose tissue. Following administrations of L-NAME, methylene blue, compound C, BIM-I, and potassium channel blockers, the level of vasodilatory action of metformin was significantly reduced (P<0.001). According to the results of this investigation, metformin significantly relaxes the thoracic aorta segments of rats. Metformin-mediated vasorelaxation involves the activation of numerous subtypes of potassium channels, including BKCa, IKCa, Kv, Kir, and K2p channels, as well as endothelium-dependent processes, including AMPK and eNOS/NO/sGS signaling pathways. Moreover, metformin-induced vasorelaxation is mediated through PVAT activation and the PKC signaling pathway.

 The cell membrane acts as a filter, allowing ions to enter and leave the cell. Ionic channels are responsible for passing ions. This task is the responsibility of the ion channel gates, and ion transfer generates the action potential. Potassium channels play a prominent role in gastrointestinal smooth muscle cells and slow-wave production. Potassium channels are involved in acid secretion and gastric contraction. Gastric functional problems such as reflux disease and motility disorder are classified as electrophysiological disorders.

 This study aimed to investigate the effect of potassium channel gates on the electrophysiology of the human gastric smooth muscle cells.

 Three states were considered for the potassium channels gate (Including physiological state, 50% blockage, and 90% blockage) to investigate the effect of the status of the gates, and a slow-wave diagram was obtained in these three states. Then, the value and the time of action potential were compared at five indicator points (initial potential, maximum spike potential, minimum valley potential, maximum plateau potential, and resting potential) in slow-wave.

 The results showed that the maximum effect of the activation parameter of the potassium channel gate (τd,Kni) was in 90% blockage compared to the physiological state, so that the maximum spike potential decreases by 2.43%. Also, a 90% blockage in the fast potassium channel gate inactivation parameter (τf,Kfi) increased the maximum spike potential by 12.6% compared to the physiological state, while the minimum valley potential increased by 3%. In addition, the τf,Kfi parameter reduced the time of occurrence of the maximum plateau potential by 7.9%.

 Potassium channels affect the slow-wave of the human gastric smooth muscle cell in spike, valley, and plateau phases. Using this method and blocking ion channels by pharmacological agents, the effect of ions in different phases of the slow-wave can be investigated. Also, it can help improve the contractile and motility disorders of the smooth muscles of the gastrointestinal tract.

Glioblastoma is an aggressive human brain malignancy with poorly understood pathogenesis. Voltage-gated potassium (Kv) channels and Matrix Metalloproteinases (MMPs) are highly expressed in malignant tumors and involved in the progression and metastasis of glioblastoma. This study aimed to determine whether a voltage-dependent potassium channel blocker could modulate astrocytes as a cell involved in the immunopathogenesis of glioblastoma. 

The cytotoxic effect of 4-Aminopyridine (4-AP) at different doses in the cell model of glioblastoma was measured by MTT assay. The ELISA technique and gelatin zymography were used to assess cytokine levels and MMP-9 after 4-AP treatment. 

Cytotoxicity analysis data indicated that cell viability reduced by increasing 4-AP level and cell growth decreased gradually by removing 4-AP from the cell medium. 4-AP inhibits the secretion of IL-6 and IL-1 (P<0.05). MMP9 activity significantly inhibits with increased 4-AP dose, compared to non-treated cells.

The reduction of cell viability, IL-6 secretion, and MMP-9 activity in an in vitro model of glioblastoma might be assumed 4-AP as an agent for chemoprevention of cancer.

Apium graveolens L. (celery) seed has been used for hypertension treatment. To provide a pharmacological basis, the vasorelaxant effect of celery seed extract was investigated in isolated rat aorta.

Wistar male rats (200-250 g) were divided into 15 groups (n=7 for each group). The vasorelaxant response of different concentrations of celery seed extract (0.05, 0.1, 0.25, 0.5, 1, and 2 mg/ml) on isolated aorta precontracted with phenylephrine (PE) or KCl was evaluated by organ bath technique. The role of endothelium, extracellular calcium influx, intracellular sources of calcium, and potassium channels in vasorelaxant effect of celery seed extract was investigated. 

The extract showed a concentration-dependent relaxation in the isolated aorta contracted with PE and KCl that was endothelium-dependent at lower concentrations. Pretreatment of aortic rings with indomethacin or L-NAME, did not affect the vasorelaxation induced by celery seed extract. The extract inhibited KCl and PE-induced contractions in cumulative calcium concentrations as well as after incubation with diltiazem in denuded aortic rings of endothelium. The relaxation induced by celery seed extract was inhibited by 4-aminopyridine.

This relaxation was mediated by inhibiting calcium influx into vascular smooth muscle cells. Also, voltage-dependent potassium channels were involved in inducing the vasorelaxant effect of celery seed extract.

In a previous work, we showed that asafoetida essential oil (AEO), from oleo-gum resin of Ferula asafoetida L. from the Apiaceae family, has a vasodilatory effect. This effect was both endothelium-dependent and endothelium-independent. The present study was designed to determine whether potassium channels and intracellular calcium release contribute to AEO-induced vasodilation. Rats' thoracic aorta were isolated and denuded. Following induction of contraction by potassium chloride (60 mM), concentration-response curve was plotted by the cumulative addition of AEO (0.625-80 µl/l to the medium of rings. The vasodilatory effect of AEO was assessed before and after addition of phenylephrine and potassium channel blockers (including barium chloride (BC), 4-aminopyridine (4A) and glibenclamide (Gl)). AEO relaxed the precontracted rings in a concentration-dependent manner (IC50=23 µl/l). All potassium channel blockers significantly attenuated the vasodilatory activity of AEO when they were added to rings medium before addition of KCl (p<0.01, 4A and Gl groups and p< 0.001, BC group vs. control group) but not after that. In contrast to K channel blockers, adding AEO before or after phenylephrine, the tension was reduced significantly (p The findings of this study indicated that the vasodilatory effect of AEO on denuded-endothelium aortic ring was mediated through activation of potassium channels and reduced intracellular calcium release.

Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.
Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone.
Local ipsilateral (20 and 40 μg, IPL) but not contralateral and ICV (4 and 8 μg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 μg, IPL or ICV) and SNAP (200 μg, IPL or ICV) increased while l-NAME (100 μg, IPL or 1 μg, ICV) and methylene blue (400 μg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 μg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test.
The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.

The goal of this study was to determine the effects of the L-type calcium channel blockers verapamil and diltiazem on the currents of voltage-gated potassium channel (fKv1.4ΔN), an N-terminal-deleted mutant of the ferret Kv1.4 potassium channel. Measurements were made using a two electrode voltage clamp technique with channels expressed stably in Xenopus oocytes. The fKv1.4ΔN currents displayed slow inactivation, with a half-inactivation potential of –38.38 mV and slow recovery from inactivation (τ = 1.90 seconds at –90 mV). The fKv1.4ΔN currents exhibited state-dependent blockade by both drugs, and the inhibition was frequency-, voltage-, and concentration-dependent, consistent with open channel block. Verapamil and diltiazem blocked fKv1.4ΔN currents with 50% inhibitory concentration (IC50) values of 260.71 ± 18.50 μmol/L and 241.04 ± 23.06 μmol/L, respectively. Verapamil accelerated the C-type inactivation rate and slowed recovery of the fKv1.4Δ N channel, while shifting the steady activation curve to the right. Blockade of fKv1.4ΔN currents by diltiazem was similar to that of verapamil, but diltiazem accelerated the decay rate of inactivation of fKv1.4ΔN currents without modifying the kinetics of current activation. The present results suggest that verapamil and diltiazem accelerate the C-type inactivation and slow the recovery of the fKv1.4ΔN channel in the open state.

Intra-peritoneal administration of riluzole has been shown to preserve the membrane properties and firing characteristics of Purkinje neurons in a rat model of cerebellar ataxia induced by 3-acetylpyridine (3-AP). However, the exact mechanism(s) by which riluzole restores the normal electrophysiological properties of Purkinje neurons is not completely understood. Changes in the conductance of several ion channels, including the BK channels, have been proposed as a neuro protective target of riluzole. In this study, the possible cellular effects of riluzole on Purkinje cells from 3-AP-induced ataxic rats that could be responsible for its neuro protective action have been investigated by computer simulations. This is a computational stimulation study. The simulation environment enabled a change in the properties of the specific ion channels as the possible mechanism of action of riluzole. This allowed us to study the resulted changes in the firing activity of Purkinje cells without concerns about its other effects and interfering parameters in the experiments. Simulations were performed in the NEURON environment (Version 7.1) in a time step of 25 μs; analyses were conducted using MATLAB r2010a (The Mathworks). Data were given as mean ± SEM. Statistical analyses were performed by the student’s t test, and differences were considered significant if p<0.05. The computational findings demonstrated that modulation of an individual ion channel current, as suggested by previous experimental studies, should not be considered as the only possible target for the neuro protective effects of riluzole to restore the normal firing activity of Purkinje cells from ataxic rats. Changes in the conductance of several potassium channels, including voltage-gated potassium (Kv1, Kv4) and big Ca2+-activated K+ (BK) channels may be responsible for the neuro protective effect of riluzole against 3-AP induced alterations in the firing properties of Purkinje cells in a rat model of ataxia.