Publications by authors named "David E Garcia"

Voltage-gated calcium channels (Ca) conduct Ca influx promoting neurotransmitters and hormone release. Ca are finely regulated by voltage-dependent and independent pathways either by G-protein-coupled receptors (GPCRs) or intramembrane lipids, respectively, in neurons and glands. Interestingly, pancreatic β-cells are abundantly innervated by both sympathetic and parasympathetic neurons, while a variety of high-voltage activated (HVA) Ca channels are present in these cells.

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Lipid regulation of ion channels is a fundamental mechanism in physiological processes as of neurotransmitter release and hormone secretion. Ceramide is a bioactive lipid proposed as a regulator of several voltage-gated ion channels including potassium channels (Kv). It is generated either de novo or by sphingomyelin (SM) hydrolysis in membranes of mammalian cells.

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Sea anemones produce venoms characterized by a complex mixture of low molecular weight compounds, proteins and peptides acting on voltage-gated ion channels. Mammal sperm cells, like neurons, are characterized by their ion channels. Calcium channels seem to be implicated in pivotal roles such as motility and capacitation.

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The FDA's approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.

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Motor learning skills are reliable indicators of behavioral acquisition and cognitive disorders. The ease with which learning skills are measured disparities the complexity of the interpretation concerning neural plasticity. Conversely, a wealth of information regarding metabolic derangements has long been reported with direct connection to high sucrose diets.

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The endocannabinoid system is found in tissues that regulate the glycemia, including adipose tissue, muscle, and pancreatic islets. Diet-induced metabolic syndrome changes the expression of the CB receptors in muscle, adipose tissue, and liver. However, it is poorly understood whether metabolic syndrome (MetS) affects the expression of CB receptors in pancreatic β cells.

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Membrane lipids are key determinants in the regulation of voltage-gated ion channels. Phosphatidylinositol 4,5-bisphosphate (PIP), a native membrane phospholipid, has been involved in the maintenance of the current amplitude and in the voltage-independent regulation of voltage-gated calcium channels (VGCC). However, the nature of the PIP regulation on VGCC has not been fully elucidated.

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There is increasing evidence that the brain resides in a state of criticality. The purpose of the present work is to characterize the dynamics of individual hippocampal CA1 pyramidal cells and to investigate how it is influenced by changes in Kv7.2/7.

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The arcuate nucleus (ARC), located at the base of hypothalamus, contains two main populations of neurons involved in the regulation of food intake and energy expenditure. The NPY neurons are orexigenic and their activation stimulates food intake while the activation of POMC neurons promote the opposite effect. Several works have tried to identify these neurons based on their electrophysiological and pharmacological characteristics.

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Voltage-dependent regulation of Ca2.2 channels by G-proteins is performed by the β (Gβ) subunit. Most studies of regulation by G-proteins have focused on channel activation; however, little is known regarding channel inactivation.

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Phosphatidylinositol-4,5-bisphosphate (PIP) is a membrane phosphoinositide that regulates the activity of many ion channels. Influx of calcium primarily through voltage-gated calcium (Ca) channels promotes insulin secretion in pancreatic β-cells. However, whether Ca channels are regulated by PIP, as is the case for some non-insulin-secreting cells, is unknown.

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The Zoanthids are an order of cnidarians whose venoms and toxins have been poorly studied. Palythoa caribaeorum is a zoanthid commonly found around the Mexican coastline. In this study, we tested the activity of P.

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Tetrodotoxin-sensitive Na(+) currents have been extensively studied because they play a major role in neuronal firing and bursting. In this study, we showed that voltage-dependent Na(+) currents are regulated in a slow manner by oxotremorine (oxo-M) and angiotensin II in rat sympathetic neurons. We found that these currents can be readily inhibited through a signaling pathway mediated by G proteins and phospholipase C (PLC) β1.

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Palythoa caribaeorum is a zoanthid (Phylum Cnidaria, class Anthozoa) commonly found in shallow waters of coral reefs along the Mexican Atlantic coast. Little is known on the pharmacological and biochemical properties of the venom components of this animal group. Toxin peptides from other cnidarian venoms, like sea anemones, target sodium and potassium voltage-gated channels.

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Several neurotransmitters and hormones acting through G protein-coupled receptors elicit a voltage-dependent regulation of CaV2.2 channels, having profound effects on cell function and the organism. It has been hypothesized that protein-protein interactions define specificity in signal transduction.

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The mevalonate-based isoprenoid biosynthetic pathway is responsible for producing cholesterol in humans and is used commercially to produce drugs, chemicals, and fuels. Heterologous expression of this pathway in Escherichia coli has enabled high-level production of the antimalarial drug artemisinin and the proposed biofuel bisabolane. Understanding the kinetics of the enzymes in the biosynthetic pathway is critical to optimize the pathway for high flux.

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A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in the Sea of Cortez, México. Its primary structure was determined by mass spectrometry and confirmed by automated Edman degradation. This conotoxin contains 40 amino acids and exhibits a novel arrangement of eight cysteine residues (C-C-C-C-CC-CC).

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GPCRs regulate Ca(V)2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of Ca(V)2.

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No mechanistic actions for piracetam have been documented to support its nootropic effects. Voltage-gated calcium channels have been proposed as a promising pharmacological target of nootropic drugs. In this study, we investigated the effect of piracetam on Ca(V)2.

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Neurotransmitters and hormones regulate Ca(V)2.2 channels through a voltage-independent pathway which is not well understood. It has been suggested that this voltage-independent inhibition is constant at all membrane voltages.

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Expression of foreign pathways often results in suboptimal performance due to unintended factors such as introduction of toxic metabolites, cofactor imbalances or poor expression of pathway components. In this study we report a 120% improvement in the production of the isoprenoid-derived sesquiterpene, amorphadiene, produced by an engineered strain of Escherichia coli developed to express the native seven-gene mevalonate pathway from Saccharomyces cerevisiae (Martin et al. 2003).

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Disruption of calcium homeostasis in epileptic cells is characterized by both short- and long-term perturbations of Ca(2+) buffering systems. Along with the Na(+)/Ca(2+) exchanger, the plasma membrane Ca(2+)-ATPase (PMCA) plays an important role in excitable cells. The involvement of PMCAs in epileptogenesis has primarily been studied in brief intervals after various stimuli; however, the specific contribution of this molecule to epileptogenesis is not yet fully understood.

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Recently, the effects of extremely low-frequency electromagnetic fields (ELF EMF) on biological systems have been extensively investigated. In this report, the influence of ELF EMF on olfactory bulb (OB) estrogen receptor-alpha (ER alpha) mRNA and -beta (ER beta) mRNA expression was studied by RT-PCR in adult female and male rats. Results reveal for the first time that ELF EMF exerted a biphasic effect on female OB ER beta mRNA gene expression, which increased during diestrous and decreased during estrous.

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It has been suggested that voltage-dependent G protein modulation of Ca(V)2.2 channels is carried out at closed states of the channel. Our purpose was to estimate the number of gating charges of Ca(V)2.

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Measurements of low molecular weight metabolites have been increasingly incorporated in the characterization of cellular physiology, qualitative studies in functional genomics, and stress response determination. The application of cutting edge analytical technologies to the measurement of metabolites and the changes in metabolite concentrations under defined conditions have helped illuminate the effects of perturbations in pathways of interest, such as the tricarboxylic acid cycle, as well as unbiased characterizations of microbial stress responses as a whole. Owing to the complexity of microbial metabolite extracts and the large number of metabolites therein, advanced and high-throughput separation techniques in gas chromatography, liquid chromatography, and capillary electrophoresis have been coupled to mass spectrometry - usually high-resolution mass spectrometry, but not exclusively - to make these measurements.

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