Acute exposure to the mitochondrial complex I toxin rotenone impairs synaptic long-term potentiation in rat hippocampal slices.

Aims: To evaluate the acute effects of the mitochondrial complex I inhibitor rotenone on rat hippocampal synaptic plasticity.

Methods: Electrophysiological field potential recordings were used to measure basal synaptic transmission and synaptic plasticity in rat coronal hippocampal slices. Synaptic long-term potentiation (LTP) was induced by high-frequency stimulation (100 Hz, 1 second × 3 at an interval of 20 seconds).

U18666A, a cholesterol-inhibition agent, modulates human neuronal nicotinic acetylcholine receptors heterologously expressed in SH-EP1 cell line.

In this study, we evaluate the effects of (3beta)-3-[2-(diethylamino)ethoxy]androst-5-en-17-one dihydrochloride (U18666A), a cholesterol synthesis/transporter inhibitor, on selected human neuronal nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the SH-EP1 cell line using whole-cell patch-clamp recordings. The results indicate that with 2-min pretreatment, U18666A inhibited different nAChR subtypes with a rank-order of potency (IC(50) of whole-cell peak current): alpha4beta2 (8.0 +/- 3.

Hydrogen peroxide mobilizes Ca2+ through two distinct mechanisms in rat hepatocytes.

Aim: Hydrogen peroxide (H2O2) is produced during liver transplantation. Ischemia/reperfusion induces oxidation and causes intracellular Ca2+ overload, which harms liver cells. Our goal was to determine the precise mechanisms of these processes.

Augmented beta cell loss and mitochondrial abnormalities in sucrose-fed GK rats.

Progressive decline of islet beta cell mass is a hallmark of type 2 diabetes, where nutritional insults are invoked in the pathologic process. Its detailed mechanisms are, however, incompletely understood. We explored the effect of sucrose diet on mitochondria in Goto Kakizaki (GK) rats, a spontaneously diabetic model.

Iptakalim, a vascular ATP-sensitive potassium (KATP) channel opener, closes rat pancreatic beta-cell KATP channels and increases insulin release.

Sulfonylureas have been the leading oral antihyperglycemic agents, and they presently continue to be the most popular antidiabetic drugs prescribed for treatment of type 2 diabetes. However, concern has arisen over the side effects of sulfonylureas on the cardiovascular system. Here, we tested the hypothesis that iptakalim, a novel vascular ATP-sensitive potassium (K(ATP)) channel opener, closes rat pancreatic beta-cell K(ATP) channels and increases insulin release.

Iptakalim modulates ATP-sensitive K(+) channels in dopamine neurons from rat substantia nigra pars compacta.

Iptakalim, a novel cardiovascular ATP-sensitive K(+) (K(ATP)) channel opener, exerts neuroprotective effects on dopaminergic (DA) neurons against metabolic stress-induced neurotoxicity, but the mechanisms are largely unknown. Here, we examined the effects of iptakalim on functional K(ATP) channels in the plasma membrane (pm) and mitochondrial membrane using patch-clamp and fluorescence-imaging techniques. In identified DA neurons acutely dissociated from rat substantia nigra pars compacta (SNc), both the mitochondrial metabolic inhibitor rotenone and the sulfonylurea receptor subtype (SUR) 1-selective K(ATP) channel opener (KCO) diazoxide induced neuronal hyperpolarization and abolished action potential firing, but the SUR2B-selective KCO cromakalim exerted little effect, suggesting that functional K(ATP) channels in rat SNc DA neurons are mainly composed of SUR1.

Novel mechanism of chronic exposure of oleic acid-induced insulin release impairment in rat pancreatic beta-cells.

A sustained, high circulating level of free fatty acids (FFAs) is an important risk factor for the development of insulin resistance, islet beta-cell dysfunction, and pathogenesis of type 2 diabetes. Here, we report a novel mechanism of chronic exposure of oleic acid (OA)-induced rat insulin release impairment. Following a 4-day exposure to 0.

Modulation of Ca2+ influx by corticotropin-releasing factor (CRF) family of peptides via CRF receptors in rat pancreatic beta-cells.

The actions of the corticotropin-releasing factor (CRF) family of peptides are mediated by the seven transmembrane-domain G-protein-coupled receptors, the CRF receptors type 1 (CRF1 receptor) and type 2 (CRF2 receptor). In a previous study, we reported that CRF, an endogenous ligand for CRF1 receptor, modulated Ca2+ influx in rat pancreatic beta-cells. In addition to CRF, other additional members of the family, urocortins, have been identified in mammals.

Sugar micro needles as transdermic drug delivery system.

We designed and fabricated an array of sugar micro needles of the length ranging from 150 micro m to 2 mm for transdermic delivery of drugs. Micro needles were molded out of maltose mixed with pharmaceutical material, being expected bio-degradable in the human skin. To test basic tolerance to the healthy human skin, a clinical experiment was carried out for 10 healthy adult volunteers.

Staphylococcal enterotoxin A modulates intracellular Ca2+ signal pathway in human intestinal epithelial cells.

We demonstrate here that staphylococcal enterotoxin A (SEA) induces an increase in intracellular calcium ([Ca2+]i) in human intestinal epithelial cells and the [Ca2+]i is released from intracellular stores. SEA-induced increase of [Ca2+]i was clearly inhibited by treatment with a nitric oxide synthase (NOS) inhibitors, N(G)-monomethyl-L-arginine and guanidine. Intestinal epithelial cells express endothelial NOS in resting cell condition, and express inducible NOS after stimulating with tumor necrosis factor (TNF)-alpha.

Role of alpha7-nicotinic acetylcholine receptors in tetanic stimulation-induced gamma oscillations in rat hippocampal slices.

Hippocampal gamma oscillations, as a form of neuronal network synchronization, are speculated to be associated with learning, memory and attention. Nicotinic acetylcholine receptor alpha7 subtypes (alpha7-nAChRs) are highly expressed in hippocampal neurons and play important roles in modulating neuronal function, synaptic plasticity, learning and memory. However, little is known about the role of alpha7-nAChRs in hippocampal gamma oscillations.

Pertussis toxin-sensitive pathway inhibits glucose-stimulated Ca2+ signals of rat islet beta-cells by affecting L-type Ca2+ channels and voltage-dependent K+ channels.

A role of pertussis toxin (PTX)-sensitive pathway in regulation of glucose-stimulated Ca2+ signaling in rat islet beta-cells was investigated by using clonidine as a selective agonist to alpha2-adrenoceptors which link to the pathway. An elevation of extracellular glucose concentration from 5.5 to 22.

2-aminoethoxydiphenyl borate inhibits agonist-induced Ca2+ signals by blocking inositol trisphosphate formation in acutely dissociated mouse pancreatic acinar cells.

Evidence suggests that 2-aminoethoxydiphenyl borate (2-APB) modulates intracellular Ca(2+) signals in a complex manner. 2-APB inhibits or potentiates intracellular Ca(2+) signals in different cell types, perhaps through different mechanisms. Here, we report a novel mechanism underlying 2-APB-induced inhibition of agonist-activated Ca(2+) oscillations in mouse pancreatic acinar cells, using patch-clamp and biochemical techniques.

Enhancement of photodynamic effect in normal rat keratinocytes by treatment with 1,25 dihydroxy vitamin D3.

Background: To better understand the pathogenesis of photodynamic therapy (PDT)-induced apoptosis cytosolic calcium [Ca2+]i was measured using cultured fetal rat keratinocytes (FRSKs). Moreover, the influence of 1,25 dihydroxy vitamin D3 (1,25(OH)2D3) with the action of increasing [Ca2+]i on the PDT effect was studied.

Methods: FRSKs were treated with a medium containing the photosensitizer, aluminum phthalocyanine tetrasulfonate (AlPcTs), and were then exposed to selective visible light derived from a halogen lamp.

Masked excitatory action of noradrenaline on rat islet beta-cells via activation of phospholipase C.

The effect of noradrenaline (NE) on rat islet beta-cells was examined. NE reduced insulin secretion from rat islets exposed to extracellular solutions containing glucose at 5.5 or 16.

Intracellular energy failure does not underlie hyperthermic spreading depressions in immature rat hippocampal slice.

Hyperthermic spreading depression (HSD) in immature rat hippocampal slices is mediated by Na+/K(+)-ATPase failure. Here, we test whether depleting intracellular ATP serves as a possible mechanism for HSD genesis. Results indicate that (1) pre-incubation with 3 mM creatine for 3 h failed to prevent hyperthermic spreading depression occurrence; and (2) intracellular ATP concentration doubled during experimental hyperthermia.

Role of mitochondrial NADH shuttle system in acute amylase secretion by acetylcholine from mouse pancreatic acinar cells.

Using the mice that lack mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), a rate limiting enzyme of the glycerol-phosphate NADH shuttle, we investigated the role of the NADH shuttle system in amylase secretion in response to acetylcholine (ACh) in pancreatic acinar cells. The pancreatic acinar cells of mGPDH-deficient mice were not different in histology and immunohistochemistry from those of wild-type mice. In both types of pancreatic acinar cells from wild-type and mGPDH-deficient mice, ACh similarly potentiated amylase secretion, measured in 30 minutes after the ACh stimulation.

Age-dependent modulation of hippocampal excitability by KCNQ-channels.

Recently, mutations of KCNQ2 or KCNQ3, members of the KCNQ-related K(+)-channel (KCNQ-channel) family, were identified as cause of benign familial neonatal convulsions (BFNC). However, the exact pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC remain to be elucidated. To clarify the age-dependent etiology of BFNC, we determined age-dependent functional switching of KCNQ-channels, GABAergic- and glutamatergic-transmission in rat hippocampus.

Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure.

Phosphodiesterase (PDE) was shown to be downregulated in the failing hearts of transplant recipients, while it was upregulated in hypertrophied hearts induced by isoproterenol and calsequesterin overexpression. We examined the time course of gene expression and the activity of PDE3 and PDE4 in an animal model of salt-induced hypertension, left ventricular hypertrophy, and congestive heart failure (CHF). Dahl salt-sensitive (DS, n = 25) and salt-resistant rats (DR, n = 25) were fed with an 8% NaCl diet after the age of 6 weeks.

Cellular function in multicellular system for hormone-secretion: electrophysiological aspect of studies on alpha-, beta- and delta-cells of the pancreatic islet.

We review a new method to explore the cellular functions in multicellular system by application of the perforated patch-clamp technique to intact pancreatic islet of Langerhans. Using this approach, the integrity of the islet is preserved and intercellular communication via gap junctions and paracrine processes are maintained. By using low-resistance patch electrodes, rapid current responses can be monitored under voltage-clamp control.

Intracellular Ca(2+) modulation of ATP-sensitive K(+) channel activity in acetylcholine-induced activation of rat pancreatic beta-cells.

We investigated the mechanism by which acetylcholine (ACh) regulates insulin secretion from rat pancreatic beta-cells. In an extracellular solution with 5.5 mM glucose, ACh increased the rate of insulin secretion from rat islets.