Excess nicotinamide increases plasma serotonin and histamine levels / 生理学报

Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).

Decreased skin function may be a risk factor for metabolic syndrome / 生理学报

The metabolic syndrome, a cluster of risk factors for cardiovascular disease, is closely related to environmental and lifestyle risk factors. Increasing evidence suggests that environmental risk factors may involve an increase in xenobiotic exposure, for example due to environmental toxins, medications, high meat intake, food additives and supplements; while lifestyle risk factors, such as sedentary lifestyles, may involve a decrease in the detoxification and elimination of xenobiotics. The skin, the body's largest organ, plays a distinct role in the detoxification and elimination of xenobiotics and the body lipid homeostasis, which is affected by sedentary lifestyle and physical activity, as well as by ambient temperature. Thus, it seems that decreased skin biotransformation and excretion, for example due to low ambient temperature and sedentary lifestyle, may be an important risk factor for metabolic syndrome. This review aims to provide insight into the role of the skin in the development of metabolic syndrome.

Chronic nicotinamide overload and type 2 diabetes / 生理学报

Type 2 diabetes is a major global health problem. It is generally accepted that type 2 diabetes is the result of gene-environmental interaction. However, the mechanism underlying the interaction is unclear. Diet change is known to play an important role in type 2 diabetes. The fact that the global high prevalence of type 2 diabetes has occurred following the spread of food fortification worldwide suggests a possible involvement of excess niacin intake. Our recent study found that nicotinamide overload and low nicotinamide detoxification may induce oxidative stress associated with insulin resistance. Based on the relevant facts, this review briefly summarized the relationship between the prevalence of type 2 diabetes and the nicotinamide metabolism changes induced by excess niacin intake, aldehyde oxidase inhibitors, liver diseases and functional defects of skin. We speculate that the gene-environmental interaction in type 2 diabetes may be a reflection of the outcome of the association of chronic nicotinamide overload-induced toxicity and the relatively low detoxification/excretion capacity of the body. Reducing the content of niacin in foods may be a promising strategy for the control of type 2 diabetes.

Potassium channels and proliferation and migration of breast cancer cells / 生理学报

Potassium channels (K(+) channels), a family of special ion channel proteins, are involved in various physiological functions. Recent data show that the abnormalities of K(+) channels are not only responsible for some neurological and cardiovascular diseases but also for channelopathies. Furthermore, many groups reported that the abnormalities of K(+) channels had shown their oncogenic potential in breast introduction and other malignant tumors, promoting proliferation, invasion and metastasis. The aim of this review is to give an updated introduction of research progress in K(+) channels associated with breast cancer.

Sodium current kinetics of transitional myocytes in Koch triangle of rabbit hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Few studies have explored the inward sodium current (INa) kinetics of transitional cardiomyocytes. This study aimed to explore the kinetics of transitional cardiomyocytes types alpha and beta.</p><p><b>METHODS</b>The whole-cell patch clamp technique was used to study the rapid INa of isolated transitional cardiomyocytes in the Koch triangle of rabbit hearts.</p><p><b>RESULTS</b>Maximal amplitude and density of INa in type alpha and type beta was (-1627 +/- 288) pA (alpha), (-35.17 +/- 6.56) pA/pF (beta) and (-3845 +/- 467) pA (alpha), (-65.64 +/- 10.23) pA/pF (beta) (P < 0.05). Steady state activation curves of INa, fitted to a Boltzmann distribution for both types, were sigmoid in shape. Half activation voltage and slope factors did not significantly differ between types at (-43.46 +/- 0.85) mV (alpha), (-41.39 +/- 0.47) mV (beta) or (9.04 +/- 0.66) mV (alpha), (11.08 +/- 0.89) mV (beta). Steady state inactivation curves of INa, fitted to a Boltzmann distribution in both types were inverse "S" shape. Half inactivation voltage and slope factors were (-109.9 +/- 0.62) mV (alpha), (-107.5 +/- 0.49) mV (beta) and (11.78 +/- 0.36) mV (alpha), (11.57 +/- 0.27) mV(beta), (P > 0.05), but time constants of inactivation were significantly different at (1.10 +/- 0.19) mV (alpha) and (2.37 +/- 0.33) ms (beta), (P < 0.05). Time constants of recovery from inactivation of INa for both types were (122.16 +/- 27.43) mV (alpha) and (103.84 +/- 28.97) ms (beta) (P < 0.05).</p><p><b>CONCLUSIONS</b>Transitional cardiomyocytes in rabbit hearts show a heterogeneous, voltage gated and time dependent fast inward sodium current. Types alpha and beta show the features of INa similar to those in slow- and fast-response myocytes, with probably better automaticity and conductivity, respectively.</p>

Effects of acute cooling/rewarming on membrane potential and K(+) currents in rat ventricular myocytes / 生理学报

The effects of acute cooling/rewarming on cardiac K(+) currents and membrane potential were investigated. Membrane potential and current were assessed with whole-cell patch-clamp technique in current- and voltage-clamp modes. When the temperature of bath solution was decreased from 25 °C; to 4 °C, the transient outward current (I(to)) was completely abolished, the sustained outward K(+) current (I(ss)) at +60 mV and the inward rectifier K(+) current (I(K1)) at -120 mV were depressed by (48.5±14.1)% and (35.7±18.2)%, respectively, and the membrane potential became more positive. After the temperature of bath solution was raised from 4 °C; to 36 °C;, the membrane potential exhibited a transient hyperpolarization and then was maintained at a stable level. In some myocytes (36 out of 58), activation of the ATP-sensitive K(+) (K(ATP)) channels after rewarming was observed. The rewarming-induced change in the membrane potential was inhibited by the Na(+)/K(+)-ATPase inhibitor ouabain (100 μmol/L), and the rewarming-elicited activation of K(ATP) channels was inhibited by the protein kinase A inhibitor H-89 (100 μmol/L). Moreover, decrease of the temperature from 25 °C; to 4 °C; did not induce any significant change in cell volume when the cell membrane potential was clamped at 0 mV. However, significant cell shrinkage with spots was observed soon after rewarming-induced activation of K(ATP) channels. These data demonstrate that acute cooling/rewarming has a profound influence on the membrane potential and K(+) currents of ventricular myocytes, and suggest that activation of K(ATP) channels may play a role in cardiac cooling/rewarming injury.

Morphological and electrophysiological properties of single myocardial cells from Koch triangle of rabbit heart / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The morphological and electrophysiological characteristics of cardiac cells in Koch triangle are still disputed. We studied the appearance and electrical properties of these diverse myocytes to elucidate their complex electrophysiological phenomena.</p><p><b>METHODS</b>Experiments were conducted using cooled charge coupling device (CCD) system and whole cell, patch clamp technique to determine the morphology, action potential and sodium current density of single viable myocytes enzymatically isolated from the Koch triangle of rabbit hearts.</p><p><b>RESULTS</b>Morphologically, cardiac cells in shape of spider, tiny spindle, slender spindle, rod and strip were observed in percentage of 3.0 +/- 0.3, 35.0 +/- 5.0, 15.0 +/- 2.0, 40.0 +/- 5.0 and 6.0 +/- 0.7 respectively. The cellular dimensions and capacitance gradually increased in the above order (all P < 0.05). Electrophysiologically, action potential configurations recorded from them were similar respectively to nodal (N), atrial nodal (AN), nodal Hisian (NH), atrial (A) and Hisian like potentials obtained from the intact atrioventricular nodal preparations. Diastolic depolarization appeared in all myocytes except for rod cells. Sodium current density increased in the order of tiny spindle, strip, rod, slender spindle cell (all P < 0.05), but could not be detected in spider-shaped cells. Linear regression analysis revealed that membrane capacitance was correlated negatively to the rate of diastolic depolarization r = -0.70, P < 0.001, but positively to maximum depolarization potential, amplitude of action potential, upstroke velocity and maximum peak value of sodium current density r = 0.84, 0.80, 0.87 and 0.75, respectively; all P < 0.001.</p><p><b>CONCLUSIONS</b>The results demonstrated that spider-shaped, spindle, rod and strip cells in Koch triangle might correspond to pacemaking, transitional, atrial and Purkinje like cells, respectively. Furthermore, tiny spindle and slender spindle cells were referred to transitional cell alpha (TCalpha) and beta (TCbeta) accordingly considering their distinctive electrical properties. Different myocytes with diverse electrical properties constituted the infrastructure of sophisticated electrophysiological phenomena in Koch triangle. In view of the prominent percentage and electrical properties, tiny spindle and slender spindle cells were presumed to play important roles.</p>

Cl⁻ channels: what role do they play in mammalian heart? / 生理学报

Cl(-) channel has been identified in heart over more than a decade. It is now known that Cl(-) channel is a super-family. The potentially important roles of cardiac Cl(-) channels have been emerging. Cardiac Cl(-) channels may play multifunctional roles in both physiological and pathophysiological conditions. Since the existence and distribution of cardiac Cl(-) channels vary with species and cardiac tissues, and blockade of Cl (-) channel with putative Cl(-) channel blockers or Cl(-) substitution has profound influence on cardiac electrical properties, it appears that the main role of cardiac Cl(-) channels may be to modulate cation channels or provide an ionic environment suitable for the activities of cation channels. So, to investigate the relationship between Cl(-) channels and cation channels may be of physiological and pathophysiological significance.

Pulmonary artery in endotoxemia rat. Effects of atrial natriuretic peptide on relaxation and constriction of aorta and pulmonary artery in endotoxemia rat / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of atrial natriuretic peptide(ANP) on constriction and relaxation of pulmonary artery and aorta in endotoxemia rat in vitro.</p><p><b>METHODS</b>24 male SD rats were randomly divided into 3 groups, control group, LPS group, ANP therapy group. These groups were injected physiologic salt water, lipopolysaccharide (LPS 2 mg/kg) and LPS + ANP(LPS 2 mg/kg, ANP 2 microg/kg) into vein respectively. After 4 hours, rats were exsanguinated to kill and aorta and pulmonary artery were separated from heart-lung for experiment of blood vessel rings. Constriction effects of aorta and pulmonary artery by norepinephrine (NE), relaxation of aorta and pulmonary artery by acetylcholine (ACh) and sodium nitroprusside SNP) observed by perfusion system in vitro.</p><p><b>RESULTS</b>Sensitiveness of NE-induced (10(-9)-10(-7) mol/L) constriction of aorta in LPS group was attenuated and EC50 was increased, but its strength (3 x 10(-7)-10(-6) mol/L) was greater comparing with control group (P < 0.01). In ANP group, the NE-induced contractility of aorta was similar to LPS group (P > 0.05). Comparing with control group, NE-induced constriction of pulmonary artery exposure to LPS was reinforced especially in 3 x 10(-7)-10(-6) mol/L of NE (P < 0.01), but its EC50 was obviously higher (P <0.05). There was no significant difference between ANP group and control group in constriction of pulmonary artery (P > 0.05). Relaxation and sensitiveness of aorta and pulmonary artery exposure to LPS were evidently improved in ANP therapy group induced by ACh and SNP respectively (P < 0.01, P < 0.05) and their EC50 markedly decreased comparing with LPS group (P < 0.01, P < 0.05) respectively.</p><p><b>CONCLUSION</b>ANP can suppress the reinforcing of NE-induced constriction of pulmonary artery exposure to LPS and partly or entirely reverse the attenuated relaxation of pulmonary artery and aorta induced by ACh and SNP in endotoxemia rats.</p>

Effect of anions and anion channel blockers on vascular tone in rat aorta / 中国应用生理学杂志

<p><b>AIM</b>To investigate the action of anions and anion channel blockers in the regulation of vascular contraction induced by norepinephrine (NE).</p><p><b>METHODS</b>NE-induced contraction was observed in rat aorta by using routine blood vascular perfusion in vitro.</p><p><b>RESULTS</b>The anion channel blockers niflumic acid (NFA) and 5-nitro-2-(3-phenoxylpropylamino)-benzoic acid (NPPB) produced inhibitory effects on NE-evoked contractions in the aorta. NE-induced contraction was not significantly changed after the extracellular Na+ was replaced by choline, in contrast, the vascular was relaxed when the extracellular Cl- was replaced by glutamate. Moreover, the vasoconstriction induced by NE was further enhanced with the replacement of the extracellular Cl- by Br-, which was still sensitive to either NFA or NPPB.</p><p><b>CONCLUSIONS</b>Anion channels play an important role in the regulation of blood vascular tone, which may be responsible for the salt-sensitivity hypertension.</p>

Effects of niflumic acid on the proliferation of human hepatoma cells / 生理学报

The purpose of this work was to investigate the effects of niflumic acid (NFA), a chloride channel blocker, on the proliferation of human hepatoma cell line (HHCC). Cell proliferation was analyzed by cell count and MTT assay. Cell cycle analysis was carried out by flow cytometry. [Ca(2+)](i) was determined by laser scanning confocal system. It was found that NFA decreased significantly the cell number and the MTT optical density (OD) of HHCC cells, and that the OD value was reversed after washout of NFA. Compared with control, NFA blocked cell cycle progression in G(1) phase. Extracellular application of NFA (100 micromol/L) induced a rapid decrease in [Ca(2+)](i). These findings demonstrate that blockage of chloride channels by NFA induces growth arrest of HHCC in G(1) phase, which may be due to the inhibition of Ca(2+)/CaM-dependent signaling pathways.

Effect of extracellular chloride concentration on deactivation kinetics of rat ClC-1 chloride channel / 生理学报

The gating mechanism of ClC-1 chloride channel was studied in this paper by heteroexpression of rat wild type ClC-1 gene in Xenopus oocytes and by two-electrode voltage clamping technique. The deactivation gating kinetic parameters were obtained by applying two exponential fitting of the deactivating currents at various extracellular chloride concentrations. It was found that decrease in extracellular chloride concentration increased the fractional amplitude of fast deactivating component, and depressed the fractional amplitude of slow deactivating component accompanied by a decrease in fast and slow deactivating time constants. These results demonstrate that the deactivation kinetic parameters of ClC-1 are largely dependent on the extracellular chloride concentration, which induces changes in channel gating.