M channel, a voltage-dependent potassium channel, has been found in a variety of neurons. It is activated near the threshold of neuron action potential,producing a primary K~+ current, namely the M-current. The M-current can be modulated by many neurotransmitters and hormones, which can influence neuron excitability, conduction and neurotransmitter release. This review discusses the signal transduction pathway from G_~ q/11 activation to intracellular calcium, membrane phospholipid and phosphokinase, and explains the mechanism of M-current modulation by neurotransmitters.

As an outward,voltage-dependent potassium channel,M type channel is crucial in the regulation of neuronal excitability;it is modulated by a variety of factors in vivo and its dysfunction often results in neuronal system diseases.Great efforts have been made to elucidate the mechanism underlying M channel modulation since its discovery decades ago.It is generally accepted that the Phospholipase C(PLC) signaling pathway plays a significant role in the M channel modulation.This review highlights the relationship between PLC signaling pathway and M channel modulation,as well as some recent progresses in the research of this field.

Receptor tyrosine kinase(RTK),a membrane receptor superfamily with intrinsic protein tyrosine kinase activity,has many members and complicated signal transduction pathways.Activation of RTKs can trigger a series of signal transduction pathways and play essential roles in modulating cell growth,proliferation,differentiation and metabolism through influencing gene transcription and expression.Activation of RTK can also rapidly modulate some cellular functions including the modulation of ion channels.Potassium channels play a critical role in stabilization of membrane potential and regulation of cellular excitability.This review highlights the rapid modulation of potassium channels by RTKs and reviews the recent progress in related research.

Aim To study the characteristics of KCNQ2/3 potassium channel expressed in CHO cells and its modulation by M_1 receptor.Methods KCNQ2 and KCNQ3 potassium channels and M_1 receptor were co-expressed in CHO cells.Whole cell patch-clamp techniques was used to observe the characteristics of KCNQ2/3 current,its modulation by the M_1 receptor,and the effects of the common potassium channel blockers.Results KCNQ2/3 current recorded in CHO cells was a slow-activation low-threshold non-inactivating,voltage-dependent outward potassium current.KCNQ2/3 current was elicited at about-60 mV,V_(1/2)(-26.8?1.2) mV and the deactivation current fitted two exponential function,with ?_(fast) of 101ms and ?_(slow) of 309 ms.The channel was not sensitive to common pharmacological blockers such as 4-AP,Ba~(2+) and TEA,but was inhibited significantly by linopirdine,with a IC_(50) of(6.5?0.83) ?mol?L~(-1).Acetylcholine suppressed the KCNQ2/3 current reversibly via M_1 receptor,with a IC_(50) of(0.7?0.05) ?mol?L~(-1).Conclusion KCNQ2 and KCNQ3 channels are the molecular basis of M-current observed in neuronal cells.KCNQ2/Q3 current expressed in CHO cells has similar characteristics as that seen in neuronal M-current.Linopirdine is a powerful blocker of KCNQ2/3 channel and acetylcholine inhibits the current by muscarinic M_1 receptor.This experiment has laid a solid basis for further study of M-current and KCNQ2/3 current,and is important for the study of neurological diseases relating to alteration of M-current,such as convulsion,epilepsy and Alzheimers disease.

Aim To study the modulation of KCNQ2/3 potassium cha nn els by extracellular pH.Methods In vitro transcription was used to synthesize cRNA of KCNQ2/3 potassium channels.The cRNA was injected into Xenopus oocytes to express the KCNQ2/3 channel.The modulation of KCNQ2/3 potass ium channels by extracellular pH was studied by two electrodes voltage clamp tec hniques.Results KCNQ2/3 currents were inhibited and current-vo ltage relationship of activation were shifted to the right with decreased extrac ellular pH. pH modulation of KCNQ2/3 currents was voltage dependent,with a more pronounced effect at more negative potentials above the activation threshold (-60 mV). Extracelluar pH also decreased activation and deactivation kinetics of KCNQ2/3 currents.Conclusion KCNQ2/3 channels, known to contr ibute to neuronal excitability, were modulated by extracelluar pH. The profound effects of the extracelluar pH exerted on KCNQ2/3 channel may play an important role during physiology neuronal activity and pathological events such a s epileptic seizures, cerebral ischemia and shock etc.

Aim To visualize the dynamics of PtdIns(4,5)P 2 hyd ro lysis and resynthesis, and modulate it by pharmacological agents wortmannin, LiC l, U73122 and neomycin. Methods We used a fusion construct of g reen fluorescent protein(GFP) with the PH domain of phospholipase C ?1(PL C ?1PH)(PLC ?1PH-GFP) known to bind PtdIns(4,5)P 2 specifically , and laser-scanning confocal microscopy to trace PtdIns(4,5)P 2 translocatio n. Results Stimulation of endogenous P 2Y receptors by ATP in CHO cells induced a reversible PLC ?1PH-GFP translocation, indicating Pt dIns(4,5)P 2 hydrolysis through the receptor-mediated phospholipase C (PLC) ac tivation. Wortmannin and LiCl did not affect the translocation of PLC ?1PH -GFP from plasma membrane to cytosol but blocked the recovery after the translo cation. The transient translocation from plasma membrane was blocked by the PLC inhibitor U73122 but was not affected by another PLC inhibitor neomycin. However , in the absence of PLC ?1PH-GFP expression, neomycin inlibited the recep tor-induced PLC hydrolysis of PtdIns(4,5)P 2.Conclusion PLC ?1PH-GFP can be used as a valuable fluorescence probe to visualize the dyn amic change of PtdIns(4,5)P 2 in living cells. Wortmannin, LiCl, U73122 and neo mycin have distinct modulation effects on PtdIns(4,5)P 2 metabolism. PLC ?1 PH,when bound to PtdIns(4,5)P 2,prevents neomycin from inhibiting PLC hydro lyzing PtdIns(4,5)P 2.

Aim To develop a sensitive, specific and accurate method for the pharmacokinetic study of QO-58 ( a novel M channel opener ) in rats after intragas-tric ( ig) and intravenous ( iv) administration. Meth-ods QO-58 was administered at the doses of 25,50, 100 mg · kg-1 ( ig ) and at single dose of 100 mg · kg-1(iv), respectively. Blood samples were obtained at intervals after each administration. Plasma samples were deproteinized with acetonitrile after addition of in-ternal standard, and detected by RP-HPLC. The main parameters of pharmacokinetics were calculated by DAS2. 1. 1 software. Results The calibration curve in plasma was linear over the range of 0. 1 ~160 mg · L-1 in rat plasma, and the limit of detection ( LOD) was 0. 1 mg · L-1 . The intra-day and inter-day RSD was less than 20%. The recovery of QO-58 in rat plas-ma was 89. 56% ~101. 38%. The concentration-time curves of QO-58 in rat palsma were consistent with the two-compartment model after both oral and intravenous administration. The main pharmacokinetic parameters for QO-58 following oral administration with three doses (25, 50, 100 mg· kg-1 ) in rat were as follows:Cmax (mg·L-1):8.25,16.29,18.27;T12β(h): 8.24, 5. 01, 5. 92; AUC0-∞ ( g · min · L-1 ):261. 94, 189. 57,90. 65. Conclusion The developed method is simple and specific, and is suitable for preclinical pharmacokinetic studies of QO-58 .

Objective To investigate the rates of depression and its risk factors in elderly hypertensive patients and healthy residents in Fuzhou.Methods 882 elderly primary hypertensive patients aged 60 years and over and 1230 healthy elderly residents were assessed by the geriatric depression scale (GDS) and a self-made general information questionnaire, and SPSS 16.0 was used to analyze data.Results The average score of depression and the incidence of depression were higher in elderly hypertensive patients than in healthy elderly residents [(12.43±5.01) vs.(11.53±5.13), 64.4％ vs.55.3％, t=-3.849, x2=16.386, P＜0.01].Compared with healthy controls, scores of depression were higher for all age groups in elderly married male patients, with low levels of education (junior middle school or below), a monthly income less than 2000 yuan, and partial or no medical insurance coverage (P＜ 0.05 for all).Scores of depression were higher in elderly hypertensive patients who had smoking or drinking habits, social activity, hobby, or physical exercise than in healthy controls, (P＜0.05 for all).Scores of depression were also higher in elderly hypertensive patients who had family support, barely enough or adequate family expenses or family support than in healthy controls, regardless of living conditions (P＜0.05 for all).Multiple stepwise regression analysis showed that risk factors for depression in elderly hypertensive patients were family support, age, medical insurance coverage, family expenses, living conditions, hobbies, and gender, while risk factors for depression in healthy elderly residents were family support, interests, medical insurance coverage, and age.Conclusions The incidence of depression is higher in elderly hypertensive patients than in health elderly people in communityin Fuzhou.Family support, hobbies, medical insurance coverage and age are the common risk factors for depression in both elderly hypertensive patients and healthy residents.Family expenses, living conditions and gender are important risk factors for depression in elderly hypertensive patients.

Objective To investigate the effects of hydrogen rich water on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and oxidative stress in rats with traumatic brain injury (TBI).Methods Ninety healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group, TBI group and hydrogen rich water treatment group (HW group), with 30 rats in each group.TBI model was reproduced by the modified Feeney weight dropping method.The skulls of rats in sham operation group underwent only craniotomy without direct hit.The rats in HW group received brain injury by hitting after craniotomy, followed by injection of hydrogen rich water (5 mL/kg) intraperitoneally once a day for 5 days after successful reproduction of the model.The rats in sham operation group and TBI group were given an equal amount of normal saline in same manner.Six rats from each group were sacrificed at 6, 12, 24, 48 hours and 5 days after evaluating neurological severity scores (NSS).The brain tissue in injured ipsilateral cortex was harvested.The activity of catalase (CAT), glutathione peroxidase (GSH-Px), and content of malondialdehyde (MDA) were determined by spectrophotometry.The expressions of mRNA and nucleoprotein of Nrf2 were determined by quantitative real-time polymerase chain reaction (RT-qPCR) and Western Blot.The pathological changes were observed with microscopy after hematoxylin and eosin (HE) staining.Results ① NSS score:compared with TBI group, NSS in HW group at 12, 24, 48 hours and 5 days were significantly decreased (12 hours: 9.83±2.32 vs.13.17±2.71, 24 hours: 9.83±2.79 vs.13.50±2.43, 48 hours: 7.50±2.07 vs.11.83±2.14, 5 days:5.50 ± 1.87 vs.10.50 ± 2.43, all P ＜ 0.05).② Compared with sham operation group, the activity of GSH-Px and CAT in TBI group were markedly declined after operation, while the MDA content was elevated significantly, especially at 24 hours [CAT (kU/g): 1.080±0.312 vs.3.571 ±0.758, GSH-Px (kU/g): 9.195±3.173 vs.32.385± 10.619, MDA (μmol/g): 12.282±2.896 vs.4.349± 1.511, all P ＜ 0.01].Compared with TBI group, the parameters in HW group were improved, and they were similar as sham operation group.③ RT-qPCR: no significant difference was found in the expression of Nrf2 mRNA at each time point in three groups.④ Western Blot: the expression of Nrf2 nucleoprotein (gray value) in TBI group was apparently higher than that in sham operation group, and peaked at 24 hours (0.703 ± 0.262 vs.0.238 ± 0.120, P ＜ 0.05), and the expression in HW group was obviously higher than that in TBI group, especially at 24 hours (1.110 ± 0.372 vs.0.703 ± 0.262, P ＜ 0.05).⑤ HE staining: the brain structure in sham operation group was found to be intact.However, there were different degrees of pathological changes at each time in TBI group, especially at 24 hours.The pathological damage of brain tissue in HW group was significantly milder.Conclusions Hydrogen rich water can up-regulate the expression of Nrf2, and reduce oxidative damage of traumatic brain injury in rats.Nrf2 can up-regulate the expression of its downstream antioxidant enzymes, which may be the mechanism of the upregulation expression of Nrf2 in the study.

Objective To investigate the quality of life (QOL) in elderly patients with chronic diseases living at home and its influencing factors.Methods 1856 elderly patients with chronic diseases living at home were selected by random cluster sampling from two communities.All patients were investigated by SF-36 questionnaire and self-made questionnaire.Results The average QOL scores were (63.8±15.1) in elderly patients with chronic diseases living at home.Scores of SF-36's eight dimensions were respectively (67.8± 22.6) in physiological function,(47.3± 39.4) in role physical,(90.2±14.3) in bodily pain,(52.3±11.9) in general health,(64.1 ± 17.1) in vitality,(74.0 ± 20.9) in social function,(49.7 ± 39.5) in emotional function,(65.0 ± 16.9) in mental health.Scores of SF-36 in each dimension were lower in patients aged 75 years and above than in patients aged 60-74 years (all P＜0.05).Scores of SF-36's dimensions including physical function,bodily pain,vitality,social function and mental health in patients aged 75 years and above were lower in males than females (all P＜0.05).Multiple stepwise regression analysis showed that the major influencing factors for the QOL in elderly patients with chronic diseases living at home were movement,hobbies,age,caregivcr,family support,number of chronic diseases,education status,and alcohol consumption (all P＜0.05).Conclusions The major influencing factors for quality of life in elderly patients with chronic diseases living at home are included demographic,behavior and family factors,etc.Comprehensive community interventions should be taken to improve the quality of life in this elderly population.