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ATP-sensitive K+ Channels (atp-sensitive + k+_channel)
Selected AbstractsInvolvement of Calmodulin in Glucagon-Like Peptide 1(7-36) Amide-Induced Inhibition of the ATP-Sensitive K+ Channel in Mouse Pancreatic ,-CellsEXPERIMENTAL PHYSIOLOGY, Issue 3 2001W. G. Ding The present investigation was designed to examine whether calmodulin is involved in the inhibition of the ATP-sensitive K+ (KATP) channel by glucagon-like peptide 1(7-36) amide (GLP-1) in mouse pancreatic ,-cells. Membrane potential, single channel and whole-cell currents through the KATP channels, and intracellular free Ca2+ concentration ([Ca2+]i) were measured in single mouse pancreatic ,-cells. Whole-cell patch-clamp experiments with amphotericin-perforated patches revealed that membrane conductance at around the resting potential is predominantly supplied by the KATP channels in mouse pancreatic ,-cells. The addition of 20 nM GLP-1 in the presence of 5 mM glucose significantly reduced the membrane KATP conductance, accompanied by membrane depolarization and the generation of electrical activity. A calmodulin inhibitor N -(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7, 20 ,M) completely reversed the inhibitory actions of GLP-1 on the membrane KATP conductance and resultant membrane depolarization. Cell-attached patch recordings confirmed the inhibition of the KATP channel activity by 20 nM GLP-1 and its restoration by 20 ,M W-7 or 10 ,M calmidazolium at the single channel level. Bath application of 20 ,M W-7 also consistently abolished the GLP-1-evoked increase in [Ca2+]i in the presence of 5 mM glucose. These results strongly suggest that the mechanisms by which GLP-1 inhibits the KATP channel activity accompanied by the initiation of electrical activity in mouse pancreatic ,-cells include a calmodulin-dependent mechanism in addition to the well-documented activation of the cyclic AMP-protein kinase A system. [source] ATP-Sensitive K+ Channels of Vascular Smooth Muscle CellsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2003WILLIAM C. COLE Ph.D. ATP-sensitive potassium channels (KATP) of vascular smooth muscle cells represent potential therapeutic targets for control of abnormal vascular contractility. The biophysical properties, regulation and pharmacology of these channels have received intense scrutiny during the past twenty years, however, the molecular basis of vascular KATP channels remains ill-defined. This review summarizes the recent advancements made in our understanding of the molecular composition of vascular KATP channels with a focus on the evidence that hetero-octameric complexes of Kir6.1 and SUR2B subunits constitute the vascular KATP subtype responsible for control of arterial diameter by vasoactive agonists. [source] Peripheral antinociceptive effect of pertussis toxin: activation of the arginine/NO/cGMP/PKG/ ATP-sensitive K+ channel pathwayEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Gerly A. C. Brito Abstract The aim of the present study was to determine the effect of pertussis toxin (PTX) on inflammatory hypernociception measured by the rat paw pressure test and to elucidate the mechanism involved in this effect. In this test, prostaglandin E2 (PGE2) administered subcutaneously induces hypernociception via a mechanism associated with neuronal cAMP increase. Local intraplantar pre-treatment (30 min before), and post-treatment (5 min after) with PTX (600 ng/paw1, in 100 µL) reduced hypernociception induced by prostaglandin E2 (100 ng/paw, in 100 µL, intraplantar). Furthermore, local intraplantar pre-treatment (30 min before) with PTX (600 ng/paw, in 100 µL) reduced hypernociception induced by DbcAMP, a stable analogue of cAMP (100 µg/paw, in 100 µL, intraplantar), which indicates that PTX may have an effect other than just Gi/G0 inhibition. PTX-induced analgesia was blocked by selective inhibitors of nitric oxide synthase (L-NMMA), guanylyl cyclase (ODQ), protein kinase G (KT5823) and ATP-sensitive K+ channel (Kir6) blockers (glybenclamide and tolbutamide). In addition, PTX was shown to induce nitric oxide (NO) production in cultured neurons of the dorsal root ganglia. In conclusion, this study shows a peripheral antinociceptive effect of pertussis toxin, resulting from the activation of the arginine/NO/cGMP/PKG/ATP-sensitive K+ channel pathway. [source] Adenosine A1 receptor activation reduces opening of mitochondrial permeability transition pores in hypoxic cardiomyocytesCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2010Fei Xiang Summary 1.,Adenosine A1 receptors (A1R) play an important role in cardioprotection against hypoxic damage and the opening of mitochondrial permeability transition pores (MPTP) is central to the regulation of cell apoptosis and necrosis. However, it is still unclear whether A1R open MPTP in hypoxic cardiomyocytes. 2.,The present study used primary cardiomyocyte cultures from neonatal rats to investigate the mechanisms of A1R activation and the effects of A1R on MPTP opening under hypoxic conditions. 3.,Hypoxia increased both MPTP opening and the production of reactive oxygen species (ROS), while decreasing cell viability and mitochondrial membrane potential (,,). The A1R agonist 2-chloro- N6 -cyclopentyladenosine (CCPA; 500 nmol/L) blocked the increase in MPTP opening and ROS production and maintained cell viability and ,, under hypoxic conditions. 4.,The protective effects of CCPA were eliminated by both the protein kinase C (PKC) inhibitor chelerythine (2 ,mol/L) and the mitochondrial ATP-sensitive K+ channel (mitoKATP) inhibitor 5-hydroxydecanoate (500 ,mol/L). Moreover, CCPA significantly increased the PKC content in both total protein and membrane protein of cardiomyocytes. 5-Hydroxydecanoate did not prevent these CCPA-induced increases in PKC. 5.,These results demonstrate that CCPA reduces MPTP opening in hypoxic cardiomyocytes, possibly by activating PKC, stabilizing ,, and reducing ROS production following the opening of mitoKATP. Consequently, fewer MPTP open. [source] Effects of sulfonylureas on mitochondrial ATP-sensitive K+ channels in cardiac myocytes: implications for sulfonylurea controversyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2006Toshiaki Sato Abstract Background Mitochondrial ATP-sensitive K+ (mitoKATP) channel plays a key role in cardioprotection. Hence, a sulfonylurea that does not block mitoKATP channels would be desirable to avoid damage to the heart. Accordingly, we examined the effects of sulfonylureas on the mitoKATP channel and mitochondrial Ca2+ overload. Methods Flavoprotein fluorescence in rabbit ventricular myocytes was measured to assay mitoKATP channel activity. The mitochondrial Ca2+ concentration was measured by loading cells with rhod-2. Results The mitoKATP channel opener diazoxide (100 µM) reversibly increased flavoprotein oxidation to 31.8 ± 4.3% (n = 5) of the maximum value induced by 2,4-dinitrophenol. Glimepiride (10 µM) alone did not oxidize the flavoprotein, and the oxidative effect of diazoxide was unaffected by glimepiride (35.4 ± 3.2%, n = 5). Similarly, the diazoxide-induced flavoprotein oxidation was unaffected both by gliclazide (10 µM) and by tolbutamide (100 µM). Exposure to ouabain (1 mM) for 30 min produced mitochondrial Ca2+ overload, and the intensity of rhod-2 fluorescence increased to 197.4 ± 7.2% of baseline (n = 11). Treatment with diazoxide significantly reduced the ouabain-induced mitochondrial Ca2+ overload (149.6 ± 5.1%, n = 11, p < 0.05 versus ouabain alone), and the effect was antagonized by the mitoKATP channel blocker 5-hydroxydecanoate (189.8 ± 27.8%, n = 5) and glibenclamide (193.1 ± 7.7%, n = 8). On the contrary, cardioprotective effect of diazoxide was not abolished by glimepiride (141.8 ± 7.8%, n = 6), gliclazide (139.0 ± 9.4%, n = 5), and tolbutamide (141.1 ± 4.5%, n = 7). Conclusions Our results indicate that glimepiride, gliclazide, and tolbutamide have no effect on mitoKATP channel, and do not abolish the cardioprotective effects of diazoxide. Therefore, these sulfonylureas, unlike glibenclamide, do not interfere with the cellular pathways that confer cardioprotection. Copyright © 2006 John Wiley & Sons, Ltd. [source] Mechanisms of ATP action on motor nerve terminals at the frog neuromuscular junctionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2005S. Grishin Abstract We have shown previously that ATP inhibits transmitter release at the neuromuscular junction through the action on metabotropic P2Y receptors coupled to specific second messenger cascades. In the present study we recorded K+ or Ca2+ currents in motor nerve endings or blocked K+ or Ca2+ channels in order to explore the nature of downstream presynaptic effectors. Endplate currents were presynaptically depressed by ATP. Blockers of Ca2+ -activated K+ -channels, such as iberiotoxin, apamin or tetraethylammonium, did not change the depressant action of ATP. By contrast, K+ channel blocker 4-aminopyridine (4-AP) and raised extracellular Ca2+ attenuated the effect of ATP. However, these effects of 4-AP and high Ca2+ were reversed by Mg2+, suggesting Ca2+ -dependence of the ATP action. Ba2+ promoted the depressant action of ATP as did glibenclamide, a blocker of ATP-sensitive K+ channels, or mild depolarization produced by 7.5 mm K+. None of the K+ channel blockers affected the depressant action of adenosine. Focal recording revealed that neither ATP nor adenosine affected the fast K+ currents of the motor nerve endings. However, unlike adenosine, ATP or UTP, an agonist of P2Y receptors, reversibly reduced the presynaptic Ca2+ -current. This effect was abolished by suramin, an antagonist of P2 receptors. Depressant effect of ATP on the endplate and Ca2+ -currents was mimicked by arachidonate, which precluded the action of ATP. ATP reduced acetylcholine release triggered by ionomycin or sucrose, suggesting inhibition of release machinery. Thus, the presynaptic depressant action of ATP is mediated by inhibition of Ca2+ channels and by mechanism acting downstream of Ca2+ entry. [source] Few cultured rat primary sensory neurons express a tolbutamide-sensitive K+ currentJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2002Violeta Ristoiu Abstract The response of dorsal root ganglion (DRG) neurons to metabolic inhibition is known to involve calcium-activated K+ channels; in most neuronal types ATP-sensitive K+ channels (KATP) also contribute, but this is not yet established in the DRG. We have investigated the presence of a KATP current using whole-cell recordings from rat DRG neurons, classifying the neurons functionally by their "current signature" (Petruska et al, J Neurophysiol 84: 2365,2379, 2000). We clearly identified a KATP current in only 1 out of 62 neurons, probably a nociceptor. The current was activated by cyanide (2 mM NaCN) and was sensitive to 100 ,M tolbutamide; the relation between reversal potential and external K+ concentration indicated it was a K+ current. In a further two neurons, cyanide activated a K+ current that was only partially blocked by tolbutamide, which may also be an atypical KATP current. We conclude that KATP channels are expressed in normal DRG, but in very few neurons and only in nociceptors. [source] Ion channel remodeling in gastrointestinal inflammationNEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2010H. I. Akbarali Abstract Background,Gastrointestinal inflammation significantly affects the electrical excitability of smooth muscle cells. Considerable progress over the last few years have been made to establish the mechanisms by which ion channel function is altered in the setting of gastrointestinal inflammation. Details have begun to emerge on the molecular basis by which ion channel function may be regulated in smooth muscle following inflammation. These include changes in protein and gene expression of the smooth muscle isoform of L-type Ca2+ channels and ATP-sensitive K+ channels. Recent attention has also focused on post-translational modifications as a primary means of altering ion channel function in the absence of changes in protein/gene expression. Protein phosphorylation of serine/theronine or tyrosine residues, cysteine thiol modifications, and tyrosine nitration are potential mechanisms affected by oxidative/nitrosative stress that alter the gating kinetics of ion channels. Collectively, these findings suggest that inflammation results in electrical remodeling of smooth muscle cells in addition to structural remodeling. Purpose,The purpose of this review is to synthesize our current understanding regarding molecular mechanisms that result in altered ion channel function during gastrointestinal inflammation and to address potential areas that can lead to targeted new therapies. [source] PERSPECTIVES: Silencing vascular smooth muscle ATP-sensitive K+ channels with caveolin-1THE JOURNAL OF PHYSIOLOGY, Issue 17 2010William C. Cole No abstract is available for this article. [source] ATP sensitivity of ATP-sensitive K+ channels: role of the , phosphate group of ATP and the R50 residue of mouse Kir6.2THE JOURNAL OF PHYSIOLOGY, Issue 3 2005Scott A. John ATP-sensitive K (KATP) channels are composed of Kir6, the pore-forming protein, and the sulphonylurea receptor SUR, a regulatory protein. We and others have previously shown that positively charged residues in the C terminus of Kir6.2, including R201 and K185, interact with the , and , phosphate groups of ATP, respectively, to induce channel closure. A positively charged residue in the N terminus, R50, is also important, and has been proposed to interact with either the , or , phosphate group of ATP. To examine this issue, we systematically mutated R50 to residues of different size, charge and hydropathy, and examined the effects on adenine nucleotide sensitivity in the absence and presence of SUR1. In the absence of SUR1, only the size of residue 50 significantly altered ATP sensitivity, with smaller side chains decreasing ATP sensitivity. In the presence of SUR1, however, hydrophathy and charge also played a role. Hydrophilic residues decreased ATP sensitivity more than hydrophobic residues for small size residues, and, surprisingly, negatively charged residues E and D preserved ATP sensitivity and increased ADP sensitivity relative to the wild-type residue R. These observations suggest that a negative charge near position 50, due to either mutation of R50 or the interaction of the , phosphate group of ATP with R50, facilitates closure of the ATP-dependent gate. Mutation of the nearby positively charged residue R54, known to be involved in stabilizing channel opening via electrostatic interactions with phosphatidylinositol 4,5-bisphosphate (PIP2), also caused increased ADP sensitivity as compared with ATP, suggesting a loss of function of ATP's , phosphate. Based on these results, we propose that a phosphate group or a negative charge at position 50 initiates channel closure by destabilizing the electrostatic interactions between negative phosphate groups of PIP2 and residues such as R54. [source] Mechanisms of Preventive Effect of Nicorandil on Ischaemia-Induced Ventricular Tachyarrhythmia in Isolated Arterially Perfused Canine Left Ventricular WedgesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Masamichi Hirose We examined effects of nicorandil on the induction of VT during acute myocardial ischaemia. Optical action potentials were recorded from the entire transmural wall of arterially perfused canine left ventricular wedges. Ischaemia was produced by arterial occlusion for 20 min. During endocardial pacing, nicorandil shortened mean action potential duration (APD) in the transmural wall before ischaemia and further shortened it during ischaemia without increasing dispersion of APD. HMR1098, a selective blocker of sarcolemmal ATP-sensitive K+ channels, inhibited the shortening of APD by nicorandil before and during ischaemia. Ischaemia decreased transmural conduction velocity (CV). Nicorandil partially restored CV to a similar extent in the absence and presence of HMR1098. In contrast, HMR1098 did not suppress the ischaemic conduction slowing in the absence of nicorandil. Nicorandil suppressed the increased dispersion of local CV during ischaemia. Isochrone maps on the initiation of VT showed that reentry in the transmural surface resulted from the excitation of the epicardial region of transmural surface. Nicorandil significantly increased the size of non-excited area in the epicardial region of the transmural wall, thereby significantly reducing the incidence of VT induced during ischaemia. HMR1098 inhibited this effect of nicorandil. These results suggest that nicorandil prevents VT during acute global ischaemia primarily by augmenting the inactivation of epicardial muscle through the activation of sarcolemmal KATP channels. [source] Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K+ channels through prostaglandin E2 in interstitial cells of Cajal from the murine small intestineBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2005Jae Yeoul Jun 1We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. 2The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. 3These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K+ channel blocker. 4NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E2 (PGE2) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE2 were blocked by glibenclamide. 5We next examined the role of deoxycholic acid in the production of PGE2 in ICC, and found that deoxycholic acid increased PGE2 production through the induction of COX-2 enzyme activity and its gene expression. 6The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K+ channels through the production of PGE2. British Journal of Pharmacology (2005) 144, 242,251. doi:10.1038/sj.bjp.0706074 [source] Multiple effects of mefenamic acid on K+ currents in smooth muscle cells from pig proximal urethraBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2003N Teramoto The effects of mefenamic acid on both membrane potential and K+ currents in pig urethral myocytes were investigated using patch-clamp techniques (conventional whole-cell, cell-attached, outside-out and inside-out configuration). In the current-clamp mode, mefenamic acid caused a concentration-dependent hyperpolarization, which was inhibited by preapplication of 1 ,M glibenclamide. In the voltage-clamp mode, mefenamic acid induced an outward current that was blocked by glibenclamide even in the presence of iberiotoxin (IbTX, 300 nM) at ,50 mV. ATP-sensitive K+ channels (KATP channels) could be activated in the same patch by mefenamic acid and levcromakalim, with the same unitary amplitude and the similar opening gating at ,50 mV in cell-attached configuration. In outside-out recording, external application of mefenamic acid activated intracellular Ca2+ -activated IbTX-sensitive large-conductance K+ channels (BKCa channels). Mefenamic acid (30 ,M) activated spontaneous transient outward currents (STOCs). In contrast, mefenamic acid (100 ,M) increased sustained outward currents, diminishing the activity of STOCs. Over the whole voltage range, mefenamic acid caused opposite effects on the membrane currents in the absence and presence of 5 ,M glibenclamide. In the presence of 10 mM 4-aminopyridine (4-AP), mefenamic acid only increased the outward currents. These results indicate that mefenamic acid increases the channel activities of two distinct types of K+ channels (i.e. BKCa channels and KATP channels) and decreased 4-AP-sensitive K+ channels in pig urethral myocytes. British Journal of Pharmacology (2003) 140, 1341,1350. doi:10.1038/sj.bjp.0705524 [source] Dualistic actions of cromakalim and new potent 2H -1,4-benzoxazine derivatives on the native skeletal muscle KATP channelBRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2003Domenico Tricarico New 2H -1,4-benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP-sensitive K+ channels (KATP) of native rat skeletal muscle fibres by using the patch-clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituents such as methyl (,CH3), ethyl (,C2H5) or propyl (,C3H7) groups, while maintaining pharmacophore groups critical for conferring agonist properties. The effects of these molecules were compared with those of cromakalim in the presence or absence of internal ATP (10,4M). In the presence of internal ATP, all the compounds increased the macropatch KATP currents. The order of potency of the molecules as agonists was ,C3H7 (DE50=1.63 × 10,8M) >,C2H5 (DE50=1.11 × 10,7M)>,CH3 (DE50=2.81 × 10,7M)>cromak-slim (DE50= 1.42 × 10,5M). Bell-shaped dose,response curves were observed for these compounds and cromakalim indicating a downturn in response when a certain dose was exceeded. In contrast, in the absence of internal ATP, all molecules including cromakalim inhibited the KATP currents. The order of increasing potency as antagonists was cromakalim (IC50=1.15 × 10,8M),CH3 (IC50=2.6 × 10,8M)>,C2H5 (IC50=4.4 × 10,8M)>,C3H7 (IC50=1.68 × 10,7M) derivatives. These results suggest that the newly synthesized molecules and cromakalim act on muscle KATP channel by binding on two receptor sites that have opposite actions. Alternatively, a more simple explanation is to consider the existence of a single site for potassium channel openers regulated by ATP which favours the transduction of the channel opening. The alkyl chains at position 2 of the 2H -1,4-benzoxazine nucleus is pivotal in determining the potency of benzoxazine derivatives as agonists or antagonists. British Journal of Pharmacology (2003) 139, 255,262. doi:10.1038/sj.bjp.0705233 [source] Alpha-2 adrenoceptors are present in rat aorta smooth muscle cells, and their action is mediated by ATP-sensitive K+ channelsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000Grasiele Fauaz The role of ,2 -adrenoceptors in the response of aorta smooth muscle rings to the ,2 -adrenoceptors agonists UK 14,304 and clonidine was studied. Stimulation by 1,10 nM UK 14,304 caused dose-dependent relaxant responses in BaCl2 -contracted endothelium-denuded aorta rings, and hyperpolarization in rings with or without endothelium, which were inhibited by yohimbine and glibenclamide, but not affected by prazosin, propranolol, apamin or iberiotoxin. At higher concentrations (10 nM,10 ,M) UK 14,304 also induced a depolarizing effect which was potentiated by yohimbine and inhibited by prazosin. These results indicate that UK 14,304 acts on ,2 -adrenoceptors at lower concentrations and on both ,1 - and ,2 -adrenoceptors above 10 nM. In rings, with or without endothelium, noradrenaline had a depolarizing effect which was inhibited by prazosin. Adrenaline did not affect the membrane potential but in the presence of prazosin caused hyperpolarization, which was inhibited by yohimbine and glibenclamide. These results indicate that noradrenaline is more selective for ,1 -, whereas adrenaline has similar affinities for ,1 - and ,2 -adrenoceptors. In aortae with endothelium, L -NNA caused a small depolarization but did not affect the hyperpolarization induced by UK 14,304, indicating that NO is not involved in that response. Glibenclamide induced a small depolarization in aortae, with or without endothelium, indicating that ATP-sensitive K+ channels may play a role in maintaining the smooth muscle's membrane potential. Our results indicate that, in rat aorta, ,2 -adrenoceptors are also present in the smooth muscle, and that these receptors act through small-conductance ATP-sensitive K+ channels. British Journal of Pharmacology (2000) 131, 788,794; doi:10.1038/sj.bjp.0703630 [source] Interaction of hydrogen sulfide with ion channelsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2010Guanghua Tang Summary 1. Hydrogen sulfide (H2S) is a signalling gasotransmitter. It targets different ion channels and receptors, and fulfils its various roles in modulating the functions of different systems. However, the interaction of H2S with different types of ion channels and underlying molecular mechanisms has not been reviewed systematically. 2. H2S is the first identified endogenous gaseous opener of ATP-sensitive K+ channels in vascular smooth muscle cells. Through the activation of ATP-sensitive K+ channels, H2S lowers blood pressure, protects the heart from ischemia and reperfusion injury, inhibits insulin secretion in pancreatic , cells, and exerts anti-inflammatory, anti-nociceptive and anti-apoptotic effects. 3. H2S inhibited L-type Ca2+ channels in cardiomyocytes but stimulated the same channels in neurons, thus regulating intracellular Ca2+ levels. H2S activated small and medium conductance KCa channels but its effect on BKCa channels has not been consistent. 4. H2S-induced hyperalgesia and pro-nociception seems to be related to the sensitization of both T-type Ca2+ channels and TRPV1 channels. The activation of TRPV1 and TRPA1 by H2S is believed to result in contraction of nonvascular smooth muscles and increased colonic mucosal Cl, secretion. 5. The activation of Cl, channel by H2S has been shown as a protective mechanism for neurons from oxytosis. H2S also potentiates N -methyl- d -aspartic acid receptor-mediated currents that are involved in regulating synaptic plasticity for learning and memory. 6. Given the important modulatory effects of H2S on different ion channels, many cellular functions and disease conditions related to homeostatic control of ion fluxes across cell membrane should be re-evaluated. [source] A Patient Suffering from Hypokalemic Periodic Paralysis Is Deficient in Skeletal Muscle ATP-sensitive K+ channelsCLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2008Sofija Jovanovi Abstract Hypokalemic periodic paralysis (HOPP) is a rare disease associated with attacks of muscle weakness and hypokalemia. In the present study, immunoprecipitation/Western blotting has shown that a HOPP patient was deficient in sarcolemmal KATP channels. Real-time RT-PCR has revealed that HOPP has decreased mRNA levels of Kir6.2, a pore-forming KATP channel subunit, without affecting the expression of other KATP channel-forming proteins. Based on these findings, we conclude that HOPP could be associated with impaired expression of Kir6.2 which leads to deficiency in skeletal muscle KATP channels, which may explain the symptoms and clinical signs of this disease. [source] | |||||||||||||