ATP-sensitive potassium channels (KATP channels) play important roles in various tissues under physiological and pathophysiological conditions by coupling cell metabolic status to electrical activity. The KATP channe l is a tetrameric complex of inwardly rectified potassium (Kir) and ATP binding protein (ABP). The Kir subunits form the channel pore, whereas ABP is required for activation and regulation. Both Kir and ABP are divided into different subu nits and the various Kir and ABP subunits “mix and match” to form KATP c hannels with different pharmacological and nucleotide sensitivities. This revie w focuses on the molecular structure, physiological roles, pathophysiological an d pharmacological properties of KATP channels in different tissues.

ATP-sensitive potassium channels (KATP channels) play important roles in various tissues tinder physiological and pathophysiological condi- conditions by coupling cell metabolic status to electrical activity. The KATP channel is a tetrameric complex of inwardly rectified potassium (Kir) and ATP binding protein (ABP). The Kir subunits form the channel pore, whereas ABP is required for activation and regulation. Both Kir and ABP are divided into different subunits and the various Kir and ABP subunits "mix and match" to form KATP channels with different pharmacological and nucleotide sensitivities. This review focuses on the molecular structure, physiological roles, pathophysiological and pharmacological proper ties of KATP channels in different tissues.

Objective To investigate the effect of KATP channel regulator on the expression of KATP subunits on the cerebral ischemia reperfusion injury(I-R) in gerbil.Methods The I-R models of gerbil were performed by occlusion common carotid artery for 10 min and reperfusion for 60 min.Forty eight gerbils were randomly divided into 8 groups: sham-operated group,I-R group,I-R+diazoxide pretreatment group,I-R+5-Hydroxydecanoate(5-HD) pretreatment group,I-R+diazoxide+5-HD pretreatment group,I-R+ pinacidil pretreatment group,I-R+glibenclamide pretreatment group,I-R+pinacidil+glibenclamide pretreatment group.Pre I-R,the gerbil of each group was injected with KATP openers or blockers correspondingly,and the expressions of Kir6.1,SUR1,SUR2 mRNA in brain tissue were detected by reverse transcriptase-polymerase chain reaction(RT-PCR).Results Compared with sham-operated group,the expression of Kir6.1 mRNA in I-R group was increased significantly.Compared with I-R group,the expression of Kir6.1 mRNA in diazoxide pretreatment group was increased significantly,whereas that in glibenclamide treatment group was decreased significantly.Compared with sham-operated group,the expression of SUR2 mRNA was increased significantly both in I-R groups and pharmacologic pretreatment groups.However,there was no difference among KATP opener and blocker groups.And the expression of SUR1 mRNA was no difference in sham-operated group,I-R group and pharmacologic pretreatment groups.Conclusion Kir6.1 mRNA is increased significantly with diazoxide pretreatment.Kir6.1 subunit plays an important role in protection of cerebral ischemia reperfusion injury.However,SUR1 mRNA and SUR2 mRNA are not influenced by the KATP regulators.

To study the mechanism and influence of pneumonia on myocardium in D-galactose(D-gal) treated mice, 36 normal male NIH mice were randomly selected and pretreated with D-gal, and then they were divided into three groups, namely control group, the first day after pneumonia group, and the third day after pneumonia group. Another group of 36 mice were pretreated with normal saline to form a general control group. The result showed that in the D-gal prtreated pneumonia mice, the degeneration of myocardial mitochondria was more pronounced, the content of MDA in myocardium was increased, and the activity of SOD and the content of ATP in the myocardium were reduced. There was a positive correlation between the content of ATP and the activity of SOD, and there was a negative correlation between the content of ATP and MDA in the myocardium. These results suggusted that the myocardial lipid peroxidation in the D-gal treated mice increased the susceptibility to the damaging factors, such as pneumonia.

Objective To study the mechanism of changes in blood gas and hemodynamics in aged rats with pneumonia. Methods Forty aged male Sprague-Dawley(SD) rats were randomly divided into three experimental groups and the control group. They were contrasted by 40 non-aged male SD rats. Hemodynamic parameters and blood gas were measured, and morphological changes of heart and lung were observed. Plasma levels of tumor necrosis factor-? (TNF-?) was examined by immunohistochemical method. Results PaO 2 and SaO 2 were lower in rats with pneumonia than those in the control rats(P

Objective: To explore the predictive value of high-sensitivity C-reactive protein (hs-CRP) levels in patients with persistent atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). Methods: A total of 77 patients of persistent AF as the first diagnosis with initial RFCA in our hospital were studied. The patients were divided into 2 groups: Recurrent group, n=27 and Non recurrent group, n=50. Basic clinical conditions were studied by Cox model analysis to screen the risk factors for AF recurrence, receiver operating characteristic (ROC) curve was conducted to assess the predictive value of hs-CRP level on AF recurrence. Results: AF recurrence was related tothe age (HR=1.126, 95% CI 1.044-1.215, P=0.002), body mass index (HR=1.297, 95% CI 1.077-1.563, P=0.006), hypertension at stage II (HR=4.142, 95% CI 1.047-16.390, P=0.043), hypertension at stage III (HR=8.595, 95%CI 1.913-38.610, P=0.005), left atrial size (HR=1.438, 95% CI 1.212-1.707, P=0.000) and hs-CRP (HR=2.026, 95% CI 1.010-4.061,P=0.047). The area under ROC curve of hs-CRP level was 0.693,P=0.005 with the cut-off point at 0.355 mg/dl. Conclusion: Persistent AF recurrence after RFCA was related to pre-operative inflammatory status; actively control pre-operative condition may reduceAF recurrence, improve prognosis and decrease adverse cardiovascular event in relevant patients.

AIM To investigate the effects of iptakalim hydrochloride(Ipt) on potassium currents in cardiomyocytes derived from guinea pig and on the specific binding of glibenclamide (Gli) with sulfonylurea receptor(SUR_ 2A ) of ATP-sensitive potassium channel (K_ ATP ) in cardiac membranes derived from Wistar rats. The effects of Ipt on the association and dissociation kinetic processes of Gli binding with SUR_ 2A of K_ ATP in cardiac preparations were also determined. METHODS The effects of Ipt on potassium currents in cardiomyocytes were observed by using patch clamp technique(whole cell recording) after application of the drug in the bath. The experiments of the ass ociation and dissociation kinetic processes of K_ ATP blocker [ 3H]Gli binding with cardiac membranes were used. RESULTS (1)The potassium current-voltage curves (I-U curves) of cardiomyocytes derived from guinea pig were upward shifted by Ipt at the concentrations of 1 and 100 ?mol?L -1 . Within 5 minutes after application of the drug, the current amplitude increased to 124.9%?9.5%(n=5)and 151.6%?11.2%(n=7)of initial current amplitude respectively(P

Objective To compare the distribution of KCNJ11 polymorphisms between elderly Chinese population with and without hypertension. Methods We examined the mutation of KCNJ11 gene by directly sequencing. Data for the present study were obtained from 250 hypertensive subjects (60 to 83 years old) as well as 250 normotensive subjects (60 to 86 years old). Results We found nine different mutations in KCNJ11, including six novel mutations (I131M, L147I, L147V, L147L, Q235H, G245C). None of the novel mutations were found in the normotensive subjects, and all the residues were conserved in other species. These sequence variants in Chinese population indicate the diversity of the human library and the complexity of hypertension. Conclusions The consistent finding of our present study provided a basis for the development of new strategies to diagnosis and treat hypertension in the elderly.

s: Objective To explore the role of microRNA-206 in peripheral blood mononuclear cells (PBMC) in the pathogenesis and development of childhood asthma. Methods Twenty-seven asthmatic children and 25 healthy controls were enrolled in the study. Peripheral blood mononuclear cells were isolated in both healthy subjects and asthmatic children in acute attack and remission stages. Total RNAs were extracted from PBMC stimulated by PMA and ionomycin, and then the RNA was reversely transcribed into cDNA. The expressions of microRNA-206 and Kruppel-like factor 4 (KLF4) and IL-17 mRNA were detected by real-time quantitative PCR (qRT-PCR) method. Results There was signiifcant difference of microRNA-206 levels among asthmatic children in attack stage and in remission stage and normal controls (F=46.58~72.81, P=0.000). Through pair-wise comparison, the microRNA-206 levels of asthmatic children in attack stage were signiifcantly lower than those in remission stage and normal control groups (P<0.01). The KLF4 and IL-17 mRNA levels of asthmatic children in attack stage were signiif-cantly higher than those in remission stage and normal control groups (P<0.01). There was no signiifcant difference of miR-206, KLF4 and IL-17 mRNA between asthmatic children in remission stage and the healthy controls (P>0.05). Furthermore, a negative correlation was found between the expression of miR-206 and KLF4 (r=–0.66, P<0.01) and between the expression of miR-206 and IL-17 mRNA (r=–0.81, P<0.01) in asthmatic children in attack stage. A positive correlation was also found between KLF4 and IL-17 mRNA in asthmatic children in attack stage (r=0.70, P<0.01). Conclusions The expression of miR-206 is decreased in asthmatic children, and miR-206 might be involved in the pathogenesis and development of asthma.

Objectives To explore the role of CD4+T cell-derived leptin in peripheral blood mononuclear cells (PBMC) in asthmatic children. Methods Peripheral blood mononuclear cells were isolated from peripheral blood of both healthy subjects and asthmatic children in attack and remission stages. CD4+T cells were purified from PBMCs by mag-netic beads and were cultured in vitro. Supernatants were used to detect the levels of leptin by ELISA. The expression of the orphan nuclear receptor (ROR)γt was detected by real-time quantitative PCR (qRT-PCR) method. Results There was significant difference in CD4+T cell-derived leptin levels of asthmatic children in attack stage (68.46±13.08 pg/ml), remis-sion stage (36.73±6.13 pg/ml) and normal controls (32.82±5.79 pg/ml) (P<0.01). Through pairwise comparison, the leptin levels in children in attack stage were significantly higher than those in remission stage and normal control groups (P<0.01). But no statistical significance was found between remission stage group and normal controls (P>0.05). The plasma leptin of children in attack stage and remission stage, as well as in normal subjects were 16.64 ± 3.53, 14.91 ± 3.24 and 13.72 ± 5.79 ng/ml respectively with no significant differences (P>0.05). The levels of RORγt mRNA were 0.341 ± 0.175, 0.089±0.028 and 0.068±0.018 in children with asthma during attack stage, remission stage and in normal children respec-tively (P<0.01). Compared to remission and normal control groups, the RORγt mRNA level of children in attack stage was markedly higher (P<0.01), but there was no significant difference between asthmatic children in remission stage and the healthy controls (P>0.05). Furthermore, the result of this study showed CD4+T cell-derived leptin positively correlated to RORγt in asthmatic children in attack stage (r=0.681, P<0.01). Conclusions CD4+T cell-derived leptin is elevated in asthmatic children in attack stage and its level is closely related to the pathological process of asthma.