Effect of dexmedetomidine on perioperative haemodynamics and early cognitive function in elderly patients undergoing laparoscopic surgery.

Introduction: Laparoscopic minimally invasive surgery has been widely used in the diagnosis and treatment of gynaecological diseases. Aim: To investigate the effect of dexmedetomidine on perioperative haemodynamics and cognitive function in elderly gynaecological patients who underwent laparoscopic surgery. Material and methods: Clinical baseline characteristics, haemodynamic parameters, renin activity, norepinephrine level, cognitive function, pain level, and sedation were compared between the 2 groups. Results: At T4 (10 min after extubation) and T5 (1 h after extubation), significant differences were found in systolic blood pressure, diastolic blood pressure, and heart rate between the 2 groups (p < 0.05); renin activity and norepinephrine level were much lower in the dexmedetomidine group than in the control group at T3 (10 min before extubation) and T4 (p < 0.05). One day before surgery, there were no significant differences in Mini-mental state examination (MMSE), visual analogue scale (VAS), and Ramsay scores between the 2 groups (p > 0.05), but the MMSE score 1 day after surgery and the Ramsay score at 12 h after surgery in the dexmedetomidine group were much higher than that in the control group (p < 0.05). Notably, at 2, 4, 12, 24, and 48 h after surgery, the VAS score in the dexmedetomidine group was significantly lower than that in the control group (p < 0.05). Conclusions: Dexmedetomidine has a better clinical effect in improving perioperative haemodynamics and early cognitive function in elderly gynaecological patients who received laparoscopic surgery.

Associations among sexuality-related factors, recent two-week morbidity and annual hospitalization in female migrant workers: a cross-sectional study in southern China.

To explore the influence of sexuality-related factors on recent two-week morbidity and annual hospitalization in female migrant workers, 880 Chinese rural-to-urban female migrant workers aged 16-57 years were studied. Clustered logistic regression analyses revealed that women who never or seldom experienced lubrication difficulties had a lower risk of recent two-week morbidity (adjusted odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.17-0.60, P< 0.001; adjusted OR = 0.35, 95% CI = 0.18-0.69, P= 0.003) than those who always experienced lubrication difficulties; women who never felt a lack of sexual interest had a significantly lower risk of annual hospitalization (adjusted OR = 0.40, 95% CI = 0.20-0.79, P= 0.009) than those who always or seldom lacked sexual interest, and women who never felt sexual satisfaction had a higher risk of annual hospitalization (adjusted OR = 3.08, 95% CI = 1.75-5.42, P< 0.001) than those who always or seldom experienced sexual satisfaction. The independent contributions of sexuality-related factors to the risk of recent two-week morbidity and annual hospitalization were 5.8% and 29.5%, respectively. This study suggests that sexuality may have a modest influence on recent two-week morbidity and a dominant impact on annual hospitalization.

The association between obesity indices and hypertension: Which index is the most notable indicator of hypertension in different age groups stratified by sex?

OBJECTIVE: This study aimed to investigate the most notable obesity index and its optimal cut-off point of hypertension in different age groups stratified by sexes among community residents in southern China. METHODS: In this cross-sectional study, 620 men and 631 women aged 18-59 years were enrolled. The independent-samples t-test and chi-square test were conducted to analyze continuous and categorical variables, respectively. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis assessed the association between the obesity indices and hypertension risk. RESULTS: Waist-stature ratio (WSR) and waist-hip ratio (WHR) were the most notable risk factors for hypertension in young men and women, respectively. The odds ratios (ORs) of hypertension risk increased with per standard deviation (SD) in WSR and WHR (WSR: OR = 2.877, 95% confidence interval [CI] = 1.602 to 5.167; WHR: OR = 10.683, 95%CI = 2.179 to 52.376). In the middle-aged group of both sexes, body mass index (BMI) was the most distinctive risk factor for hypertension, the ORs of hypertension risk increased with per SD in BMI (men: OR = 2.297, 95%CI = 1.683 to 3.136; women: OR = 1.810, 95%CI = 1.338 to 2.450). ROC curve analysis demonstrated WSR and PI were better indicators than other indices among young men, and WSR was the best marker among young women. However, BMI and WC were the most sensitive markers in middle-aged men and women, respectively. CONCLUSIONS: In this Chinese population, the association of obesity indices and hypertension is inconsistent in different age groups and sexes. It is important to choose appropriate indicators for specific groups of people.

Association between obesity and sickness in the past two weeks among middle-aged and elderly women: A cross-sectional study in Southern China.

OBJECTIVES: Sickness situation in the past two weeks, an indicator of health service needs, is an increasing major health concern. However, data on the relationship between obesity and two-week morbidity in the female population, particularly in middle-aged and elderly women, is sparse. The present study aimed to examine the association between obesity and two-week morbidity among middle-aged and elderly women in Southern China, and to explore the independent contributions of socio-demographic variables, health-related factors, and obesity to two-week morbidity. METHODS: In total, 2364 middle-aged and elderly women were included in this cross-sectional, community-based survey. Obesity was assessed using body mass index (BMI). The outcome variable was sickness situation over the past two weeks (two-week morbidity). Clustered logistic regression was applied to analyze the independent contribution of obesity to two-week morbidity. RESULTS: Approximately 14.6% of participants experienced sickness in the past two weeks. Obesity (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.02-2.12) was significantly associated with two-week morbidity and its independent contribution accounted for 3.7%, lower than that of socio-demographic variables (73.7%) and health-related factors(22.6%). CONCLUSIONS: Some degree of correlation was observed between obesity and two-week morbidity among middle-aged and elderly women in Southern China, which can be used as a reference for health-related decision-making.

Functional status and annual hospitalization in multimorbid and non-multimorbid older adults: a cross-sectional study in Southern China.

BACKGROUND: Hospitalization over the last one year, an indicator of health service utilization, is an important and costly resource in older adult care. However, data on the relationship between functional status and annual hospitalization among older Chinese people are sparse, particularly for those with and without multimorbidity. In this study,we aimed to examine the association between functional status and annual hospitalization among community-dwelling older adults in Southern China, and to explore the independent contributions of socio-demographic variables, lifestyle and health-related factors and functional status to hospitalization in multimorbid and non-multimorbid groups. METHODS: This cross-sectional, community-based survey, studied 2603 older adults aged 60 years and above. Functional status was assessed by Functional Independence Measure (FIM). The outcome variable was any hospitalization over the last one year (annual hospitalization). Clustered logistic regression was used to analyze the independent contributions of FIM domains to annual hospitalization. RESULTS: Only in the multimorbid group, did the risk of annual hospitalization decrease significantly with increasing FIM score in walk domain (adjusted OR = 0.80 per SD increase, 95% CI = 0.70-0.91, P = 0.001) and its independent contribution accounted for 24.62%, more than that of socio-demographic variables (18.46%). However, among individuals without multimorbidity, there were no significant associations between FIM domains and annual hospitalization; thus, no independent contribution to the risk of hospitalization was observed. CONCLUSIONS: There exist some degree of correlation between functional status and annual hospitalization among older adults in Southern China, which might be due to the presence of multimorbidity with advanced age.

Association of erythrocyte parameters with metabolic syndrome in the Pearl River Delta region of China: a cross sectional study.

OBJECTIVE: Increasing studies have reported that erythrocyte parameters, including red blood cells (RBCs), haematocrit (HCT), haemoglobin (Hb) and red blood cell distribution width (RDW), are associated with metabolic syndrome (MetS) in adults worldwide. However, the association, stratified by sex, remains to be elucidated, particularly in the Pearl River Delta region of China. Therefore, our aim was to explore the association of erythrocyte parameters with MetS, stratified by sex, in the Pearl River Delta region of China. METHODS: In this cross sectional study, 2161 men and 2511 women were enrolled. MetS was diagnosed using a modified version of the Adult Treatment Panel III criteria. Logistic regression analyses were performed to calculate adjusted ORs of erythrocyte parameters associated with MetS stratified by sex. RESULTS: The prevalence of MetS was higher in women than in men (35.2%vs26.7%). RBC, HCT, Hb and RDW values increased linearly with the number of MetS components from 0 to 5 identified in both men and women. Among men, the ORs of MetS risk increased across the tertiles of Hb (Q2: OR=1.921, 95% CI=1.170 to 3.151; Q3: OR=1.992, 95%CI=1.198 to 3.312). Men in the highest tertiles of RDW had a 2.752-fold increased risk of suffering from MetS compared with those in the reference group. Among women, the ORs of MetS risk also increased across the tertiles of Hb (Q2: OR=1.538, 95%CI=1.008 to 2.348; Q3: OR=1.665, 95%CI=1.075 to 2.578). Women in the highest tertiles of RBC had a 1.718-fold increased risk of experiencing MetS compared with those in the reference group. CONCLUSIONS: MetS was more prevalent in women than in men. The association between erythrocyte parameters and MetS differed between the sexes. RBC and Hb were identified as risk factors for MetS in women and Hb and RDW as risk factors in men.

Clear cell hepatocellular carcinoma diagnosed by bile duct brushing cytology.

Clear cell hepatocellular carcinoma (CCHCC) is an uncommon morphologic variant of HCC and rarely invades into the main bile ducts. Here we describe a case of CCHCC that was diagnosed by bile duct brushing cytology. Liquid-based preparation of brushing specimen showed clusters of atypical epithelial cells with abundant clear cytoplasm, round nuclei, and occasional intranuclear inclusions. The tumor cells were positive for HepPar-1 and arginase 1, suggestive of their hepatic origin. The overall morphologic and immunophenotypic features were consistent with CCHCC. The cytological diagnosis was confirmed by histopathologic examination of the resected tumor.

Sensitivity of cloned muscle, heart and neuronal voltage-gated sodium channels to block by polyamines: a possible basis for modulation of excitability in vivo.

Spermidine and spermine, are endogenous polyamines (PAs) that regulate cell growth and modulate the activity of numerous ion channel proteins. In particular, intracellular PAs are potent blockers of many different cation channels and are responsible for strong suppression of outward K (+) current, a phenomenon known as inward rectification characteristic of a major class of KIR K (+) channels. We previously described block of heterologously expressed voltage-gated Na (+) channels (NaV) of rat muscle by intracellular PAs and PAs have recently been found to modulate excitability of brain neocortical neurons by blocking neuronal NaV channels. In this study, we compared the sensitivity of four different cloned mammalian NaV isoforms to PAs to investigate whether PA block is a common feature of NaV channel pharmacology. We find that outward Na (+) current of muscle (NaV 1.4), heart (NaV 1.5), and neuronal (NaV 1.2, NaV 1.7) NaV isoforms is blocked by PAs, suggesting that PA metabolism may be linked to modulation of action potential firing in numerous excitable tissues. Interestingly, the cardiac NaV 1.5 channel is more sensitive to PA block than other isoforms. Our results also indicate that rapid binding of PAs to blocking sites in the NaV 1.4 channel is restricted to access from the cytoplasmic side of the channel, but plasma membrane transport pathways for PA uptake may contribute to long-term NaV channel modulation. PAs may also play a role in drug interactions since spermine attenuates the use-dependent effect of the lidocaine, a typical local anesthetic and anti-arrhythmic drug.

Vasopressin and oxytocin excite MCH neurons, but not other lateral hypothalamic GABA neurons.

Neurons that synthesize melanin-concentrating hormone (MCH) colocalize GABA, regulate energy homeostasis, modulate water intake, and influence anxiety, stress, and social interaction. Similarly, vasopressin and oxytocin can influence the same behaviors and states, suggesting that these neuropeptides may exert part of their effect by modulating MCH neurons. Using whole cell recording in MCH-green fluorescent protein (GFP) transgenic mouse hypothalamic brain slices, we found that both vasopressin and oxytocin evoked a substantial excitatory effect. Both peptides reversibly increased spike frequency and depolarized the membrane potential in a concentration-dependent and tetrodotoxin-resistant manner, indicating a direct effect. Substitution of lithium for extracellular sodium, Na(+)/Ca(2+) exchanger blockers KB-R7943 and SN-6, and intracellular calcium chelator BAPTA, all substantially reduced the vasopressin-mediated depolarization, suggesting activation of the Na(+)/Ca(2+) exchanger. Vasopressin reduced input resistance, and the vasopressin-mediated depolarization was attenuated by SKF-96265, suggesting a second mechanism based on opening nonselective cation channels. Neither vasopressin nor oxytocin showed substantial excitatory actions on lateral hypothalamic inhibitory neurons identified in a glutamate decarboxylase 67 (GAD67)-GFP mouse. The primary vasopressin receptor was vasopressin receptor 1a (V1aR), as suggested by the excitation by V1aR agonist [Arg(8)]vasotocin, the selective V1aR agonist [Phe(2)]OVT and by the presence of V1aR mRNA in MCH cells, but not in other nearby GABA cells, as detected with single-cell RT-PCR. Oxytocin receptor mRNA was also detected in MCH neurons. Together, these data suggest that vasopressin or oxytocin exert a minimal effect on most GABA neurons in the lateral hypothalamus but exert a robust excitatory effect on presumptive GABA cells that contain MCH. Thus, some of the central actions of vasopressin and oxytocin may be mediated through MCH cells.

Kisspeptin directly excites anorexigenic proopiomelanocortin neurons but inhibits orexigenic neuropeptide Y cells by an indirect synaptic mechanism.

The neuropeptide kisspeptin is necessary for reproduction, fertility, and puberty. Here, we show strong kisspeptin innervation of hypothalamic anorexigenic proopiomelanocortin (POMC) cells, coupled with a robust direct excitatory response by POMC neurons (n > 200) to kisspeptin, mediated by mechanisms based on activation of a sodium/calcium exchanger and possibly opening of nonselective cation channels. The excitatory actions of kisspeptin on POMC cells were corroborated with quantitative PCR data showing kisspeptin receptor GPR54 expression in the arcuate nucleus, and the attenuation of excitation by the selective kisspeptin receptor antagonist, peptide 234. In contrast, kisspeptin inhibits orexigenic neuropeptide Y (NPY) neurons through an indirect mechanism based on enhancing GABA-mediated inhibitory synaptic tone. In striking contrast, gonadotropin-inhibiting hormone (GnIH and RFRP-3) and NPY, also found in axons abutting POMC cells, inhibit POMC cells and attenuate the kisspeptin excitation by a mechanism based on opening potassium channels. Together, these data suggest that the two central peptides that regulate reproduction, kisspeptin and GnIH, exert a strong direct action on POMC neurons. POMC cells may hypothetically serve as a conditional relay station downstream of kisspeptin and GnIH to signal the availability of energy resources relevant to reproduction.

Neuromedin B and gastrin-releasing peptide excite arcuate nucleus neuropeptide Y neurons in a novel transgenic mouse expressing strong Renilla green fluorescent protein in NPY neurons.

Neuropeptide Y (NPY) is one of the most widespread neuropeptides in the brain. Transgenic mice were generated that expressed bright Renilla green fluorescent protein (GFP) in most or all of the known NPY cells in the brain, which otherwise were not identifiable. GFP expression in NPY cells was confirmed with immunocytochemistry and single-cell reverse transcription-PCR. NPY neurons in the hypothalamic arcuate nucleus play an important role in energy homeostasis and endocrine control. Whole-cell patch clamp recording was used to study identified arcuate NPY cells. Primary agents that regulate energy balance include melanocortin receptor agonists, AgRP, and cannabinoids; none of these substances substantially influenced electrical properties of NPY neurons. In striking contrast, neuropeptides of the bombesin family, including gastrin-releasing peptide and neuromedin B, which are found in axons in the mediobasal hypothalamus and may also be released from the gut to signal the brain, showed strong direct excitatory actions at nanomolar levels on the NPY neurons, stronger than the actions of ghrelin and hypocretin/orexin. Bombesin-related peptides reduced input resistance and depolarized the membrane potential. The depolarization was attenuated by several factors: substitution of choline for sodium, extracellular Ni(2+), inclusion of BAPTA in the pipette, KB-R7943, and SKF96365. Reduced extracellular calcium enhanced the current, which reversed around -20 mV. Together, these data suggest two mechanisms, activation of nonselective cation channels and the sodium/calcium exchanger. Since both NPY and POMC neurons, which we also studied, are similarly directly excited by bombesin-like peptides, the peptides may function to initiate broad activation, rather than the cell-type selective activation or inhibition reported for many other compounds that modulate energy homeostasis.

Agouti-related peptide and MC3/4 receptor agonists both inhibit excitatory hypothalamic ventromedial nucleus neurons.

Anorexigenic melanocortins decrease food intake by activating MC3/MC4 receptors (MC3/4R); the prevailing view is that the orexigenic neuropeptide agouti-related peptide (AgRP) exerts the opposite action by acting as an antagonist at MC3/MC4 receptors. A total of 370 hypothalamic ventromedial nucleus (VMH) glutamatergic neurons was studied using whole-cell recording in hypothalamic slices from a novel mouse expressing green fluorescent protein (GFP) under control of the vesicular glutamate transporter 2 (vGluT2) promoter. Massive numbers of GFP-expressing VMH dendrites extended out of the core of the nucleus into the surrounding cell-poor shell. VMH dendrites received frequent appositions from AgRP-immunoreactive axons in the shell of the nucleus, but not the core, suggesting that AgRP may influence target VMH neurons. alpha-MSH, melanotan II (MTII), and selective MC3R or MC4R agonists were all inhibitory, reducing the spontaneous firing rate and hyperpolarizing vGluT2 neurons. The MC3/4R antagonist SHU9119 was excitatory. Unexpectedly, AgRP did not attenuate MTII actions on these neurons; instead, these two compounds showed an additive inhibitory effect. In the absence of synaptic activity, no hyperpolarization or change in input resistance was evoked by either MTII or AgRP, suggesting indirect actions. Consistent with this view, MTII increased the frequency of spontaneous and miniature IPSCs. In contrast, the mechanism of AgRP inhibition was dependent on presynaptic inhibition of EPSCs mediated by G(i)/G(o)-proteins, and was attenuated by pertussis toxin and NF023, inconsistent with mediation by G(s)-proteins associated with MC receptors. Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors.

Vasopressin increases locomotion through a V1a receptor in orexin/hypocretin neurons: implications for water homeostasis.

Water homeostasis is a critical challenge to survival for land mammals. Mice display increased locomotor activity when dehydrated, a behavior that improves the likelihood of locating new sources of water and simultaneously places additional demands on compromised hydration levels. The neurophysiology underlying this well known behavior has not been previously elucidated. We report that the anti-diuretic hormone arginine-vasopressin (AVP) is involved in this response. AVP and oxytocin directly induced depolarization and an inward current in orexin/hypocretin neurons. AVP-induced activation of orexin neurons was inhibited by a V1a receptor (V1aR)-selective antagonist and was not observed in V1aR knock-out mice, suggesting an involvement of V1aR. Subsequently activation of phospholipase Cbeta triggers an increase in intracellular calcium by both calcium influx through nonselective cation channels and calcium release from calcium stores in orexin neurons. Intracerebroventricular injection of AVP or water deprivation increased locomotor activity in wild-type mice, but not in transgenic mice lacking orexin neurons. V1aR knock-out mice were less active than wild-type mice. These results suggest that the activation of orexin neurons by AVP or oxytocin has an important role in the regulation of spontaneous locomotor activity in mice. This system appears to play a key role in water deprivation-induced hyperlocomotor activity, a response to dehydration that increases the chance of locating water in nature.

GABA excitation in mouse hilar neuropeptide Y neurons.

Neuropeptide Y-containing interneurons in the dentate hilar area play an important role in inhibiting the activity of hippocampal circuitry. Hilar cells are often among the first lost in hippocampal epilepsy. As many types of neurons are found in the hilus, we used a new transgenic mouse expressing green fluorescent protein (GFP) in a subset of neurons that colocalized neuropeptide Y (NPY), somatostatin (SST), and GABA for whole-cell, perforated, and cell-attached recording in 240 neurons. As these neurons have not previously been identifiable in live slices, they have not been the focus of physiological analysis. Hilar NPY neurons showed modest spike frequency adaptation, a large 15.6 +/- 1.0 mV afterhyperpolarization, a mean input resistance of 335 +/- 26 M Omega, and were capable of fast-firing. Muscimol-mediated excitatory actions were found in a nominally Ca(2+)-free/high-Mg(2+) bath solution using cell-attached recording. GABA(A) receptor antagonists inhibited half the recorded neurons and blocked burst firing. Gramicidin perforated-patch recording revealed a GABA reversal potential positive to both the resting membrane potential and spike threshold. Together, these data suggest GABA is excitatory to many NPY cells. NPY and SST consistently hyperpolarized and reduced spike frequency in these neurons. No hyperpolarization of NPY on membrane potential was detected in the presence of tetrodotoxin, AP5, CNQX and bicuculline, supporting an indirect effect. Under similar conditions, SST hyperpolarized the cells, suggesting a direct postsynaptic action. Depolarizing actions of GABA and GABA-dependent burst-firing may synchronize a rapid release of GABA, NPY, and SST, leading to pre- and postsynaptic inhibition of excitatory hippocampal circuits.

Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and postsynaptic mechanisms: tonic depression of the hypothalamic arousal system.

Neurons that release neuropeptide Y (NPY) have important effects on hypothalamic homeostatic regulation, including energy homeostasis, and innervate hypocretin neurons. Using whole-cell patch-clamp recording, we explored NPY actions on hypocretin cells identified by selective green fluorescent protein expression in mouse hypothalamic slices. NPY reduced spike frequency and hyperpolarized the membrane potential of hypocretin neurons. The NPY hyperpolarizing action persisted in tetrodotoxin (TTX), was mimicked by Y1 receptor-selective agonists [Pro34]-NPY and [D-Arg25]-NPY, and was abolished by the Y1-specific antagonist BIBP3226 [(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amide], consistent with a direct activation of postsynaptic Y1 receptors. NPY induced a current that was dependent on extracellular potassium, reversed near the potassium equilibrium potential, showed inward rectification, was blocked by extracellular barium, and was abolished by GDP-betaS in the recording pipette, consistent with a G-protein-activated inwardly rectifying K+ (GIRK) current. [Pro34]-NPY evoked, and BIBP3226 blocked, the activation of the GIRK-type current, indicating mediation by a Y1 receptor. NPY attenuated voltage-dependent calcium currents mainly via a Y1 receptor subtype. BIBP3226 increased spontaneous spike frequency, suggesting an ongoing Y1 receptor-mediated NPY inhibition. In TTX, miniature EPSCs were reduced in frequency but not amplitude by NPY, NPY13-36, and [D-Trp32]-NPY, but not by [Pro34]-NPY, suggesting the presynaptic inhibition was mediated by a Y2/Y5 receptor. NPY had little effect on GABA-mediated miniature IPSCs but depressed spontaneous IPSCs. Together, these data support the view that NPY reduces the activity of hypocretin neurons by multiple presynaptic and postsynaptic mechanisms and suggest NPY axons innervating hypocretin neurons may tonically attenuate hypocretin-regulated arousal.

Inhibitory effects of berberine on ion channels of rat hepatocytes.

AIM: To examine the effects of berberine, an isoquinoline alkaloid with a long history used as a tonic remedy for liver and heart, on ion channels of isolated rat hepatocytes. METHODS: Tight-seal whole-cell patch-clamp techniques were performed to investigate the effects of berberine on the delayed outward potassium currents (I(K)), inward rectifier potassium currents (I(K1)) and Ca(2+) release-activated Ca(2+) currents (I(CRAC)) in enzymatically isolated rat hepatocytes. RESULTS: Berberine 1-300 micromol/L reduced I(K) in a concentration-dependent manner with EC(50) of 38.86+/-5.37 micromol/L and n(H) of 0.82+/-0.05 (n = 8). When the bath solution was changed to tetraethylammonium (TEA) 8 mmol/L, I(K) was inhibited. Berberine 30 micromol/L reduced I(K) at all examined membrane potentials, especially at potentials positive to +60 mV (n = 8, P<0.05 or P<0.01 vs control). Berberine had mild inhibitory effects on I(K1) in rat hepatocytes. Berberine 1-300 micromol/L also inhibited I(CRAC) in a concentration-dependent fashion. The fitting parameters were EC(50) = 47.20+/-10.86 micromol/L, n(H) = 0.71+/-0.09 (n = 8). The peak value of I(CRAC) in the I-V relationship was decreased by berberine 30 micromol/L at potential negative to -80 mV (n = 8, P<0.05 vs control). But the reverse potential of I(CRAC) occurred at voltage 0 mV in all cells. CONCLUSION: Berberine has inhibitory effects on potassium and calcium currents in isolated rat hepatocytes, which may be involved in hepatoprotection.

Effects of berberine on potassium currents in acutely isolated CA1 pyramidal neurons of rat hippocampus.

The effects of berberine, an isoquinoline alkaloid with antiarrhythmic action, on voltage-dependent potassium currents were studied in acutely isolated CA1 pyramidal neurons of rat hippocampus by using the whole-cell patch-clamp techniques. Berberine blocked transient outward potassium current (IA) and delayed rectifier potassium current (IK) in a concentration-dependent manner with EC50 of 22.94+/-4.96 microM and 10.86+/-1.06 microM, Emax of 67.47+/-4.00% and 67.14+/-1.79%, n of 0.77+/-0.08 and 0.96+/-0.07, respectively. Berberine 30 microM shifted the steady-state activation curve and inactivation curve of IA to more negative potentials, but mainly affected the inactivation kinetics. Berberine 30 microM positively shifted the steady-state activation curve of IK. These results suggested that blockades on K+ currents by berberine are preferential for IK, and contribute to its protective action against ischemic brain damage.

Electrophysiological effects of anthopleurin-Q on rat hepatocytes.

AIM: To study the effects of AP-Q on CCl(4)-induced acute liver injury, delayed outward potassium current (I(K)), inward rectifier potassium current (I(K1)) and calcium release-activated calcium current (I(CRAC)) in isolated rat hepatocytes. METHODS: A single dose of CCl(4) (10 microg/mL, ip) was injected to induce acute liver injury in rats. Serum aminotransferase activities were determined. Whole cell patch-clamp techniques were used to investigate the effects of AP-Q on delayed outward potassium current (I(K)), inward rectifier potassium current (I(K1)) and calcium release-activated calcium current (I(CRAC)). RESULTS: AP-Q (3.5 and 7 microg/kg) pretreatment significantly reduced ALT and AST activities. AP-Q 0.1-100 nM produced a concentration-dependent increase of I(K) with EC(50) value of 5.55+/-1.8 nM (n=6). AP-Q 30 nM shifted the I-V curve of I(K) leftward and upward. CCl(4) 4 mM decreased I(K) current 28.6+/-6.5% at 140 mV. After exposure to CCl(4) for 5 min, AP-Q 30 nM attenuated the decrease of I(K) induced by CCl(4) close to normal amplitude. AP-Q 0.01-100 nM had no significant effect on either inward or outward components of I(K1) at any membrane potential examined. AP-Q 0.1-100 nM had no significant influence on the peak amplitude of I(CRAC), either, and did not affect the shape of its current voltage curve. CONCLUSION: AP-Q has a protective effect on CCl(4)-induced liver injury, probably through selectively increased I(K) in hepatocytes.

Perforated patch recording of L-type calcium current with beta-escin in guinea pig ventricular myocytes.

AIM: To establish a perforated patch recording (PPR) mode with beta-escin and compare L-type calcium current (I(Ca,L)) recorded under PPR and normal whole-cell recording (WCR) condition in isolated guinea-pig ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. beta-escin was added to the pipette solution to perforate the cell membrane and obtain PPR mode. I(Ca,L) was recorded using PPR and WCR techniques. RESULTS: beta-Escin 20, 25, and 30 micromol/L could permeabilize the cell membrane and obtain PPR mode. With beta-escin 25 micromol/L, the success rate was highest (16/17, 94 %) and the time required for permibilization was 2-15 (8+/-4) min. Run-down of I(Ca,L) was considerably slower in PPR than in WCR condition. The amplitude of I(Ca,L) was decreased by 36 % at 20 min after the formation of WCR, while it was slowly decreased by 8 % at 30 min after the formation of PPR. The current-voltage relation (I-V) curves, activation and inactivation curves of I(Ca,L) were not significantly different between WCR and PPR. The inactivation rate of ICa,L was slower in PPR than in WCR, the faster inactivation time constant (tau(f)) was longer in PPR than in WCR at membrane potentials of -20 mV -- +10 mV (n=6, P<0.05), and the slower time constant (tau(s)) was also longer in PPR than in WCR at membrane potentials of -10 mV to +10 mV (n=6, P<0.05). There was no significant difference between the activation rate in WCR and PPR. CONCLUSION: Using beta-escin 25 micromol/L can easily obtain stable PPR in isolated guinea-pig ventricular myocytes, and this method is useful in dealing with channels, which show run-down under normal WCR such as L-type Ca channel.