ATP-dependent Potassium Channels Research Articles

The role of ATP-dependent potassium channels and nitric oxide system in the neuroprotective effect of preconditioning

To study a role of ATP-dependent potassium channels (K+ATP) in the neuroprotective effect of ischemic (IP) and pharmacological (PP) preconditioning and evaluate the dynamics of blood nitric oxide (NO) metabolites in cerebral ischemia. A model of ischemic stroke induced by the electrocoagulation of a middle cerebral artery (MCA) branch was used in male rats (n=86). Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, and diazoxide, a potassium channel activator, were used. IP and PP were performed 24 h before MCA occlusion. Blood concentrations of NO, NO3- and NO2-were measured 5, 24 and 72 h after occlusion. IP decreased a lesion area by 37% (p<0/05) and the preliminary introduction ofglibenclamide levelled the effect of IP. A protective effect of PP was similar to that of IP. A decrease in oxygenated R-conformers of Hb-NO and a reverse increase in non-oxygenated T-conformers as well as NO3- и NO2-were noted 5h after MCA occlusion. In the first 24 h after MCA occlusion, contents of NO3- and NO2- returned to normal values. There were changes in the concentrations of Hb-NO complexes as well, with the predominance of R-conformers and minimal contents of T-conformers. Moreover, the correlations between K+ATP channel blockade and the decrease in serum NO3- and NO2 were found (p<0/03). The neuroprotective effect of preconditioning is caused by the activation of K+ATP channels. An analysis of NO metabolite concentrations in the blood of rats with IP suggests that Hb-NO complexes belonging to R-conformers deposit and carry NO in tissues releasing NO accumulated via R→T transfer in conditions of ischemia.

Agonist and Antagonist Effects of ATP-Dependent Potassium Channel on Penicillin Induced Epilepsy in Rats

Doc. Dr. Recep Ozmerdivenli, Duzce Universitesi Tip Fakultesi Fizyoloji Anabilim Dali, Kat: 2 81620 Duzce Turkiye, Tel. 0532 426 98 98 Email. rozmerdivenli@hotmail.com Gelis Tarihi: 11.04.2015 • Kabul Tarihi: 09.06.2015 ABSTRACT AIM: Epileptic seizures occur when the balance between stimulating and inhibiting systems in the brain tends to deterioration in the direction of stimulating systems dominancy. Antiepileptic effect of potassium (K) channel openers has been shown in in vitro and in vivo studies. The purpose of this study is to investigate K ATP channel agonist (pinacidil) and antagonists (glibenclamide) acute effects on experimental epilepsy models.

Nicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel

ObjectiveIt has been confirmed that adipokines are associated with atherosclerosis. Cigarette smoking was found to possibly influence adipokine secretion. However, the precise role of smoking in adipokine secretion and the underlying mechanisms are largely unknown. The aim of this study was to determine whether nicotine, the principal active ingredient of cigarettes, can influence adipokine secretion and its potential mechanism. MethodsThe present study consecutively enrolled 96 men, including 50 smokers with early atherosclerosis and 46 nonsmokers. Serum adipokines, including leptin, resistin, and visfatin, were determined with enzyme-linked immunosorbent assay in all participants. Furthermore, the effect of nicotine on secretion of these adipokines was examined in differentiated 3T3-L1 preadipocytes under the conditions of ATP-dependent potassium (KATP) channel blocked or unblocked. ResultsCompared with the control group, serum levels of leptin, resistin, and visfatin in smokers were significantly higher. In 3T3-L1 adipocytes, nicotine treatment significantly increased the levels of these adipokines (P = 0.014, 0.001, and 0.029, respectively). When the KATP channel was blocked, secretion of resistin and visfatin was reduced (P < 0.001), but no change was found in the leptin secretion (P = 0.522). ConclusionsNicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel.

3-(2,2,2-trimethylhydrazinium) propionate: the role of ATP-dependent potassium channels in cardioprotection effect

The work evaluated the influence of 3-(2,2,2-trimethylhydrazinium) propionate per square necrotic myocardium of the left ventricle and the level Troponin I serum during acute coronary occlusion (60 minutes) followed by reperfusion (90 min) in anesthetized rabbits. It is shown that distant and pharmacological preconditioning 3 (2,2,2-trimethylhydrazinium) propionate reduce necrosis zone 3 and 1,5 times, respectively. Found participation ATP dependent potassium channels (K-ATР channels) of endothelial and inducible NO-synthase in the implementation of the cytoprotective effect of distant preconditioning and 3-(2,2,2-trimethylhydrazinium) propionate, indicating that the implementation of the mechanism of pharmacological preconditioning in his cardioprotection action.

Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1.

Proper glycemic control is one of the most important goals in perioperative patient management. Insulin secretion from pancreatic β-cells in response to an increased blood glucose concentration plays the most critical role in glycemic control. Several animal and human studies have indicated that volatile anesthetics impair glucose-stimulated insulin secretion (GSIS). A convincing GSIS model has been established, in which the activity of ATP-dependent potassium channels (KATP) under the control of intracellular ATP plays a critical role. We previously reported that pimonidazole adduct formation and stabilization of hypoxia-inducible factor-1α (HIF-1α) were detected in response to glucose stimulation and that MIN6 cells overexpressing HIF-1α were resistant to glucose-induced hypoxia. Genetic ablation of HIF-1α or HIF-1β significantly inhibited GSIS in mice. Moreover, we previously reported that volatile anesthetics suppressed hypoxia-induced HIF activation in vitro and in vivo.To examine the direct effect of volatile anesthetics on GSIS, we used the MIN6 cell line, derived from mouse pancreatic β-cells. We performed a series of experiments to examine the effects of volatile anesthetics (sevoflurane and isoflurane) on GSIS and demonstrated that these compounds inhibited the glucose-induced ATP increase, which is dependent on intracellular hypoxia-induced HIF-1 activity, and suppressed GSIS at a clinically relevant dose in these cells.

Modulation of Potassium Channel Activity in the Balance of ROS and ATP Production by Durum Wheat Mitochondria-An Amazing Defense Tool Against Hyperosmotic Stress.

In plants, the existence of a mitochondrial potassium channel was firstly demonstrated about 15 years ago in durum wheat as an ATP-dependent potassium channel (PmitoKATP). Since then, both properties of the original PmitoKATP and occurrence of different mitochondrial potassium channels in a number of plant species (monocotyledonous and dicotyledonous) and tissues/organs (etiolated and green) have been shown. Here, an overview of the current knowledge is reported; in particular, the issue of PmitoKATP physiological modulation is addressed. Similarities and differences with other potassium channels, as well as possible cross-regulation with other mitochondrial proteins (Plant Uncoupling Protein, Alternative Oxidase, Plant Inner Membrane Anion Channel) are also described. PmitoKATP is inhibited by ATP and activated by superoxide anion, as well as by free fatty acids (FFAs) and acyl-CoAs. Interestingly, channel activation increases electrophoretic potassium uptake across the inner membrane toward the matrix, so collapsing membrane potential (ΔΨ), the main component of the protonmotive force (Δp) in plant mitochondria; moreover, cooperation between PmitoKATP and the K+/H+ antiporter allows a potassium cycle able to dissipate also ΔpH. Interestingly, ΔΨ collapse matches with an active control of mitochondrial reactive oxygen species (ROS) production. Fully open channel is able to lower superoxide anion up to 35-fold compared to a condition of ATP-inhibited channel. On the other hand, ΔΨ collapse by PmitoKATP was unexpectedly found to not affect ATP synthesis via oxidative phosphorylation. This may probably occur by means of a controlled collapse due to ATP inhibition of PmitoKATP; this brake to the channel activity may allow a loss of the bulk phase Δp, but may preserve a non-classically detectable localized driving force for ATP synthesis. This ability may become crucial under environmental/oxidative stress. In particular, under moderate hyperosmotic stress (mannitol or NaCl), PmitoKATP was found to be activated by ROS, so inhibiting further large-scale ROS production according to a feedback mechanism; moreover, a stress-activated phospholipase A2 may generate FFAs, further activating the channel. In conclusion, a main property of PmitoKATP is the ability to keep in balance the control of harmful ROS with the mitochondrial/cellular bioenergetics, thus preserving ATP for energetic needs of cell defense under stress.

Modulation of neural firing through intracellular ATP dynamics governed by energy feedback from the vascular system

We propose a simple model for neuro-glio-vascular interactions to emphasize on the role of energy feedback from the vascular system in brain's computations [1,2]. In [1], we introduced a bidirectional communication within a detailed biophysical model of neuron-astrocyte-vessel. We now compress this model to just two modules: the neuron and the 'energy' module. The energy module is a lumped representation of the astrocyte-vessel system; it receives neural firing activity as input and controls intracellular neuronal energy (ATPi) levels as a feedback. The model comprises of a quadratic integrate and fire neuron with a dynamic threshold, Vth, which further depends on the ATPi dynamics. Vth is high during ATPi deficit, making the neuron least excitable and vice versa for high ATPi conditions. The underlying principle of modeling Vth as a function of ATPi is based on the experiments describing the role of KATP channels in governing neural excitability [3]. These channels are ATP-dependent potassium channels and are open when ATPi is low, resulting in a depolarized membrane potential of the neuron during metabolically compromised states such as hypoxia [3]. The neuron model parameters are adapted to that of mammalian cortical pyramidal neuron [4]. Furthermore, ATPi dynamics are also modeled similar to [4], where ATPi consumption directly depends on neural spiking activity. The production rate of ATPi, ep is a crucial model parameter representing the local vascular activity. A wide range of neural dynamic behaviors: phasic bursting, tonic bursting and continuous spiking are observed by varying ep and external input current Iext. Furthermore, simulation of a network consisting of such energy-dependent neural units (Figure ​(Figure1A.)1A.) depicts that ep could modulate the Local field potential (LFP) frequencies and amplitudes (Figure ​(Figure1B.).1B.). Interestingly, low frequency LFP dominates under low ep conditions and could represent seizure-like activity observed in epilepsy. Although conventional neuroscience considers unidirectional influences from neurons to small vessels, there have been proposals that highlight the reverse influence from the vessels to the neurons [1,2] . The proposed 'neuron-energy' unit may be treated as a building-block in large scale models of neurovascular networks. Figure 1 A. Implemented network configuration with n (=1000) neurons, i synapses with c (=20%) connectivity. B. Simulated LFP at both high (=10) and low (=3) ep. C. & D. depicts spectrograms for low and high ep, respectively.

Abstract 18437: Women and Ischemic Heart Disease: Which Role for Katp Channels?

Background: In the last decades, scientists have been studying the pathophysiology of ischemic heart disease (IHD) in women. In fact, as it is well known, in women IHD differs in term of pathogenesis, symptoms and prognosis. Different risk factors and mechanisms of disease may be at work in women. Genetic polymorphisms (SNP) for coronary ion channels may be involved in IHD susceptibility. In particular, the SNP rs5215 for Kir6.2 subunit of ATP-dependent potassium (KATP) channels has been proposed as a protective factor in IHD susceptibility, mostly in women. Aim and methods: To confirm the preliminary encouraging results on the protective role SNP rs5215_GG in IHD susceptibility for women, we enrolled 460 consecutive patients (144 women) with an indication to undergo coronary angiography for suspected ischemic heart disease, performing intracoronary functional tests in patients showing anatomically normal arteries to evaluate coronary microvascular function. We analyzed SNPs relative to the Kir6.2 subunit of KATP channels. Results: Among 460 patients, 330 presented with CAD (72 women), 68 with microvascular dysfunction (39 women) and 62 with anatomically and functionally normal coronary arteries (33 women). The SNP rs5215_GG was found to be more frequent in women compared to men (21/144 -14.6%, vs. 36/316 -11.3%; p=0.36). In particular, rs5215_GG was more frequent in ladies with anatomically and functionally normal coronary arteries compared with women presenting CAD (9/33 -27.2% vs. 7/72 -9.7%; p=0.037), whereas there was no difference between men in normal and CAD groups. Discussion and conclusion: Our data validate the hypothesis that rs5215_GG could reduce susceptibility to IHD in women, since it is more frequent in ladies presenting anatomically and functionally normal coronary arteries. The results suggest that KATP channels with rs5215_GG could be protective against IHD. Our data endorse the prospect of associations between SNP encoding coronary ion channels and IHD, validating the idea that ion channels play in coronary homeostasis and that their polymorphisms act in IHD genesis.

Levosimendan. A promising future drug for refractory cardiac failure in children?

Intravenous positive inotropic agents play an important role in treating acute decompensation of patients with heart failure due to left ventricular systolic dysfunction. Levosimendan is a new positive inotropic agent having ATP-dependent potassium-channel opening, and calcium-sensitizing effects, which increases cardiac contractility and performance along with vasodilatatory action without increasing myocardial oxygen demand. We report a case of a 12-year-old girl with viral myocarditis, dilated cardiomyopathy, biventricular failure with severe left ventricular dysfunction, refractory to standard management, and who was successfully improved with levosimendan.

Intrathecal CD4(+) and CD8(+) T-cell responses to endogenously synthesized candidate disease-associated human autoantigens in multiple sclerosis patients.

MS pathology is potentially orchestrated by autoreactive T cells, but the antigens recognized remain unknown. A novel APC/T-cell platform was developed to determine intrathecal CD4(+) and CD8(+) T-cell responses to candidate MS-associated autoantigens (cMSAg) in clinically isolated syndrome (CIS, n = 7) and MS (n = 6) patients. Human cMSAg encoding open reading frames (n = 8) were cloned into an Epstein-Barr virus (EBV)-based vector to express cMSAg at high levels in EBV-transformed B-cells (BLCLs). Human cMSAg cloned were myelin-associated and -oligodendrocyte glycoprotein, myelin basic protein, proteolipid protein, ATP-dependent potassium channel ATP-dependent inwards rectifying potassium channel 4.1, S100 calcium-binding protein B, contactin-2, and neurofascin. Transduced BLCLs were used as autologous APC in functional T-cell assays to determine cMSAg-specific T-cell frequencies in cerebrospinal fluid derived T-cell lines (CSF-TCLs) by intracellular IFN-γ flow cytometry. Whereas all CSF-TCL responded strongly to mitogenic stimulation, no substantial T-cell reactivity to cMSAg was observed. Contrastingly, measles virus fusion protein-specific CD4(+) and CD8(+) T-cell clones, used as control of the APC/T-cell platform, efficiently recognized transduced BLCL expressing their cognate antigen. The inability to detect substantial T-cell reactivity to eight human endogenously synthesized cMSAg in autologous APC do not support their role as prominent intrathecal T-cell target antigens in CIS and MS patients early after onset of disease.

Effects of levosimendan on cellular metabolic alterations in patients with septic shock: a randomised controlled study

Mitochondrial dysfunction and consequent cellular energetic failure play a key role in the development of sepsis-related organs failure. Levosimendan, by a calcium-sensitizing mechanism increases myocardial contractility while simultaneously exerting vasodilatory properties via activation of ATP-dependent potassium channels (KATP) [1].

Hydrogen sulfide induces hyperpolarization and decreases the exocytosis of secretory granules of rat GH3 pituitary tumor cells

The aim of the present study was to evaluate the effects of hydrogen sulfide (H2S) on the membrane potential, action potential discharge and exocytosis of secretory granules in neurosecretory pituitary tumor cells (GH3). The H2S donor – sodium hydrosulfide (NaHS) induced membrane hyperpolarization, followed by truncation of spontaneous electrical activity and decrease of the membrane resistance. The NaHS effect was dose-dependent with an EC50 of 152 μM (equals effective H2S of 16–19 μM). NaHS effects were not altered after inhibition of maxi conductance calcium-activated potassium (BK) channels by tetraethylammonium or paxilline, but were significantly reduced after inhibition or activation of ATP-dependent potassium channels (KATP) by glibenclamide or by diazoxide, respectively. In whole-cell recordings NaHS increased the amplitude of KATP currents, induced by hyperpolarizing pulses and subsequent application of glibenclamide decreased currents to control levels. Using the fluorescent dye FM 1–43 exocytosis of secretory granules was analyzed in basal and stimulated conditions (high K+ external solution). Prior application of NaHS decreased the fluorescence of the cell membrane in both conditions which links with activation of KATP currents (basal secretion) and activation of KATP currents and BK-currents (stimulated exocytosis). We suggest that H2S induces hyperpolarization of GH3 cells by activation of KATP channels which results in a truncation of spontaneous action potentials and a decrease of hormone release.

Structural and Dynamic Changes in Mitochondria of Rat Myocardium under Acute Hypoxic Hypoxia: Role of Mitochondrial ATP-Dependent Potassium Channel.

The ultrastructure and spatial localization of mitochondria (MC) in the myocardium of rats exposed to a 30-min hypoxic hypoxia were investigated. The mitochondrial structure was found to undergo changes; however, marked necrotic injuries were not observed. Changes occurring in the myocardium are aimed at the intensification of energy processes. This shows up as an increase in the number of MC in the subsarcolemmal zone of the myocardium and changes in the surface of the sublemmal membrane due to its bending around mitochondria, which improves the diffusion of oxygen into MC. In addition, the division of MC is enhanced, which partially explains the increase in their total number. In structurally altered MC with intact membrane, electron dense formations with small diameter appear, which probably represent newly formed organelles (microMC). In normoxia, changes of this kind do not occur. It was found that the ATP-dependent K+ channel is involved in the regulation of the morphological state of MC under hypoxic hypoxia. The activator of the channel diazoxide increases the number of newly formed microMC, and the channel inhibitor 5HD significantly prevents their formation. Possible mechanisms of structural and dynamic changes in rat myocardial MC under acute hypoxic hypoxia are discussed.

Hypotensive effect of alpha-lipoic acid after a single administration in rats

Objective:The effect of alpha-lipoic acid on blood pressure was investigated many times in chronic studies, but there are no studies on the effect of this compound after a single administration. Alpha-lipoic acid is a drug used in diabetic neuropathy, often in obese patients, to treat hypertension. Therefore, knowledge of the potential antihypertensive effect of alpha-lipoic acid even after a single dose and possibly too much pressure reduction is interesting and useful.Methods:The mechanism of the hypotensive effect of alpha-lipoic acid was examined in normotensive rats in vivo after a single intraperitoneal administration, blood pressure in the left carotid artery of the rats was measured prior to the administration of the compounds (alpha- lipoic acid and/or glibenclamide) and 80 min thereafter.Results:Alpha-lipoic acid at a dosage of 50 mg/kg b.w. i.p. significantly decreased the blood pressure from the 50th min after drug administration. This cardiovascular effect of this compound was reversed by glibenclamide, a selective KATP blocker. Glibenclamide alone at this dose did not significantly affect the blood pressure. Statistical significance was evaluated using two-way ANOVA.Conclusion:This suggests that alpha-lipoic acid affects ATP-dependent potassium channels. It is possible that this is an indirect effect of hydrogen sulfide because alpha-lipoic acid can increase its concentration. The results obtained in this study are very important because the patients taking alpha-lipoic acid may be treated for co-existing hypertension. Therefore, the possibility of blood pressure lowering by alpha-lipoic acid should be taken into account, although it does not lead to excessive orthostatic hypotension.

PP90 - Hydrogen sulfide preconditioning mitigates LPS-induced endoplasmic reticulum stress in rat hepatocytes through upregulation of HO-1 and opening the ATP-dependent potassium channel

PP90 - Hydrogen sulfide preconditioning mitigates LPS-induced endoplasmic reticulum stress in rat hepatocytes through upregulation of HO-1 and opening the ATP-dependent potassium channel

Slow potentials encode intercellular coupling and insulin demand in pancreatic beta cells.

Ion fluxes constitute a major integrative signal in beta cells that leads to insulin secretion and regulation of gene expression. Understanding these electrical signals is important for deciphering the endogenous algorithms used by islets to attain homeostasis and for the design of new sensors for monitoring beta cell function. Mouse and human islets were cultured on multielectrode arrays (MEAs) for 3-13days. Extracellular electrical activities received on each electrode were continuously amplified and recorded for offline characterisation. Differential band-pass filtering of MEA recordings of mouse islets showed two extracellular voltage waveforms: action potentials (lasting 40-60ms) and very robust slow potentials (SPs, lasting 800-1,500ms), the latter of which have not been described previously. The frequency of SPs directly correlated with glucose concentration, peaked at 10mmol/l glucose and was further augmented by picomolar concentrations of glucagon-like peptide-1. SPs required the closure of ATP-dependent potassium channels as they were induced by glucose or glibenclamide but were not elicited by KCl-induced depolarisation. Pharmacological tools and the use of beta cell specific knockout mice showed that SPs reflected cell coupling via connexin 36. Moreover, increasing and decreasing glucose ramps showed hysteresis with reduced glucose sensitivity during the decreasing phase. SPs were also observed in human islets and could be continuously recorded over 24h. This novel electrical signature reflects the syncytial function of the islets and is specific to beta cells. Moreover, the observed hysteresis provides evidence for an endogenous algorithm naturally present in islets to protect against hypoglycaemia.

Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro.

Levosimendan is a positive inotropic drug for the treatment of acute decompensated heart failure (HF). Clinical trials showed that levosimendan was particularly effective in HF due to myocardial infarction. Myocardial necrosis induces a strong inflammatory response, involving chemoattractants guiding polymorphonuclear neutrophils (PMN) into the infarcted myocardial tissue. Our aim was to examine whether levosimendan exhibits anti-inflammatory effects on human adult cardiac myocytes (HACM) and human heart microvascular endothelial cells (HHMEC). Cardiac myocytes and endothelial cells were stimulated with interleukin-1β (IL)-1β (200 U/ml) and treated with levosimendan (0.1-10 µM) for 2-48 hours. IL-1β strongly induced expression of IL-6 and IL-8 in HACM and E-selectin and intercellular adhesion molecule-1 (ICAM-1) in HHMEC and human umbilical vein endothelial cells (HUVEC). Treatment with levosimendan strongly attenuated IL-1β-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs. Levosimendan treatment further reduced adhesion of PMN to activated endothelial cells under both static and flow conditions by approximately 50 %. Incubation with 5-hydroxydecanoic acid, a selective blocker of mitochondrial ATP-dependent potassium channels, partly abolished the above seen anti-inflammatory effects. Additionally, levosimendan strongly diminished IL-1β-induced reactive oxygen species and nuclear factor-κB (NF-κB) activity through inhibition of S536 phosphorylation. In conclusion, levosimendan exhibits anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. These findings could explain, at least in part, the beneficial effects of levosimendan after myocardial infarction.

Adiponectin may be a biomarker of early atherosclerosis of smokers and decreased by nicotine through KATP channel in adipocytes

ObjectivePlasm adiponectin is decreased in smokers. Adiponectin is emerging as a potential key molecular marker in atherosclerosis and other cardiovascular diseases. The aim of this study was to investigate the association between serum adiponectin levels and early atherosclerosis in smokers. Furthermore, the role of the KATP channel in the down-regulation of adiponectin by smoking was preliminarily explored. MethodsWe consecutively enrolled 96 men, including 50 smokers with atherosclerosis and 46 nonsmokers. Serum adiponectin was detected with enzyme-linked immunosorbent assay - in all participants. Large (C1) and small (C2) artery elasticity indices and carotid intima-media thickness (IMT) were measured as evaluation indexes of early atherosclerosis in smokers. Finally, the effect of nicotine via ATP-dependent potassium (KATP) channels on adiponectin secretion by 3T3-L1 preadipocytes was examined in vitro. ResultsAdiponectin levels of smokers were statistically negatively correlated to IMT (r = −.440; P < 0.001) and positively correlated to C1 (r = 0.448; P < 0.001) as well as C2 (r = 0.426; P = 0.002). In 3-T3-L1 preadipocytes, nicotine treatment significantly decreased adiponectin levels (P = 0.003), whereas the adiponectin level was rescued by the inhibition of KATP channel (P < 0.001). ConclusionSerum adiponectin level was an independent predictor of early atherosclerosis in smokers. Nicotine might decrease adiponectin in part through altering KATP channels in adipocytes.

Recent progress in pharmacogenomics of repaglinide

Repaglinide is one of the most commonly used oral antidiabetic drugs. It can lower postprandial plasma glucose by means of initiating early-phase insulin release through closing the ATP-dependent potassium channels. Phamacogenomics is a branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism. The progress of phamacogenomic study on repaglinide is summarized in this article. (Chin J Endocrinol Metab, 2015, 31: 185-187) Key words: Diabetes mellitus; Phamacogenomics; Repaglinide

The effects of ATP-dependent potassium channel opener; pinacidil, and blocker; glibenclamide, on the ischemia induced arrhythmia in partial and complete ligation of coronary artery in rats.

Electrical inhomogeneity between ischemic and non ischemic myocardium is the basis of arrhythmia which occurs following coronary artery occlusion. The leakage of potassium from the ischemic region to the non ischemic region is very effective in the generation of these arrhythmias. The aim of this study is to research the effect of ATP-dependent potassium (KATP) channel blocker (glibenclamide) and opener (pinacidil) on ischemia induced arrhythmia in the presence of small and large infarct sizes. In this study Sprague-Dawley male rats of 8-9 months of age were used. Ischemia was produced by the partial ligation of left coronary artery ramus descending (PL) for smaller infarct and complete ligation of this artery (CL) for larger infarct for 30 min. The arrhythmia score which was calculated from the duration and type of arrhythmia was significantly higher in animals which had a larger infarct area than the animals which had a smaller infarct. Glibenclamide increased the rate of arrhythmia in animals having smaller infarct but not in animals having larger infarct. Pinacidil did not affect the occurrence of arrhythmia in either group. There was a significant difference in the infarct size and risk of infarct zone between animals which had small and large infarct sizes. The effect of glibenclamide and pinacidil on the arrhythmias differed depend on decrease of infarct size. Glibenclamide is not effective to decrease ischemia induced arrhythmia in the presence of small and pinacidil in large ischemic zone.