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  • 1
    Electronic Resource
    Electronic Resource
    350 Main Street , Malden , MA 02148 , USA , and 9600 Garsington Road , Oxford OX4 2XG , UK . : Blackwell Science Inc
    Journal of cardiovascular electrophysiology 15 (2004), S. 0 
    ISSN: 1540-8167
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The endothelium plays a vital role in the control of vascular functions, including modulation of tone; permeability and barrier properties; platelet adhesion and aggregation; and secretion of paracrine factors. Critical signaling events in many of these functions involve an increase in intracellular free Ca2+ concentration ([Ca2+]i). This rise in [Ca2+]i occurs via an interplay between several mechanisms, including release from intracellular stores, entry from the extracellular space through store depletion and second messenger-mediated processes, and the establishment of a favorable electrochemical gradient. The focus of this review centers on the role of potassium channels and membrane potential in the creation of a favorable electrochemical gradient for Ca2+ entry. In addition, evidence is examined for the existence of various classes of potassium channels and the possible influence of regional variation in expression and experimental conditions. (J Cardiovasc Electrophysiol, Vol. 15, pp. 598-610, May 2004)
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP27 and PACAP38) on isolated parasympathetic neurons of rat intracardiac and submandibular ganglia were examined under voltage clamp using whole-cell patch-clamp recording techniques. VIP and PACAP (≤ 10 n m) selectively and reversibly increased the affinity of nicotinic acetylcholine receptor channels (nAChRs) for their agonists resulting in a potentiation of acetylcholine (ACh)-evoked whole-cell currents at low agonist concentrations. VIP-induced potentiation was observed with either ACh or nicotine as the cholinergic agonist. The VIP- but not the PACAP-induced potentiation of ACh-evoked currents was inhibited by [Ac-Tyr1, D-Phe2]-GRF 1–29, amide (100 n m), a selective antagonist of VPAC1 and VPAC2 receptors; whereas the PACAP38- but not the VIP-induced potentiation was inhibited by 100 n m PACAP6–38, a PAC1 and VPAC2 receptor antagonist. The signal transduction pathway mediating VIP- and PACAP-induced potentiation of nicotinic ACh-evoked currents involves a pertussis toxin (PTX)-sensitive G-protein. Intracellular application of 200 μm GTPγS or GDPβS inhibited VIP-induced potentiation of ACh-evoked whole-cell currents. GTPγS alone potentiated ACh- and nicotine-evoked currents and the magnitude of these currents was not further increased by VIP or PACAP. The G-protein subtype modulating the neuronal nAChRs was examined by intracellular dialysis with antibodies directed against αo, αi-1,2, αi-3 or β G-protein subunits. Only the anti-Gαo and anti-Gβ antibodies significantly inhibited the effect of VIP and PACAP on ACh-evoked currents. The potentiation of ACh-evoked currents by VIP and PACAP may be mediated by a membrane-delimited signal transduction cascade involving the PTX-sensitive Go protein.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of auxiliary calcium channel subunits on the expression and functional properties of high-voltage activated (HVA) calcium channels have been studied extensively in the Xenopus oocyte expression system, but are less completely characterized in a mammalian cellular environment. Here, we provide the first systematic analysis of the effects of calcium channel β and α2–δ subunits on expression levels and biophysical properties of three different types (Cav1.2, Cav2.1 and Cav2.3) of HVA calcium channels expressed in tsA-201 cells. Our data show that Cav1.2 and Cav2.3 channels yield significant barium current in the absence of any auxiliary subunits. Although calcium channel β subunits were in principle capable of increasing whole cell conductance, this effect was dependent on the type of calcium channel α1 subunit, and β3 subunits altogether failed to enhance current amplitude irrespective of channel subtype. Moreover, the α2–δ subunit alone is capable of increasing current amplitude of each channel type examined, and at least for members of the Cav2 channel family, appears to act synergistically with β subunits. In general agreement with previous studies, channel activation and inactivation gating was regulated both by β and by α2–δ subunits. However, whereas pronounced regulation of inactivation characteristics was seen with the majority of the auxiliary subunits, effects on voltage dependence of activation were only small (〈 5 mV). Overall, through a systematic approach, we have elucidated a previously underestimated role of the α2–δ1 subunit with regard to current enhancement and kinetics. Moreover, the effects of each auxiliary subunit on whole cell conductance and channel gating appear to be specifically tailored to subsets of calcium channel subtypes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Although neural progenitor cells (NPCs) may provide a source of new neurons to alleviate neural trauma, little is known about their electrical properties as they differentiate. We have previously shown that single NPCs from the adult rat hippocampus can be cloned in the presence of heparan sulphate chains purified from the hippocampus, and that these cells can be pushed into a proliferative phenotype with the mitogen FGF2 [Chipperfield, H., Bedi, K.S., Cool, S.M. & Nurcombe, V. (2002) Int. J. Dev. Biol., 46, 661–670]. In this study, the active and passive electrical properties of both undifferentiated and differentiated adult hippocampal NPCs, from 0 to 12 days in vitro as single-cell preparations, were investigated. Sparsely plated, undifferentiated NPCs had a resting membrane potential of ≈ −90 mV and were electrically inexcitable. In 〉 70%, ATP and benzoylbenzoyl-ATP evoked an inward current and membrane depolarization, whereas acetylcholine, noradrenaline, glutamate and GABA had no detectable effect. In Fura-2-loaded undifferentiated NPCs, ATP and benzoylbenzoyl-ATP evoked a transient increase in the intracellular free Ca2+ concentration, which was dependent on extracellular Ca2+ and was inhibited reversibly by pyridoxalphosphate-6-azophenyl-2′-4′-disulphonic acid (PPADS), a P2 receptor antagonist. After differentiation, NPC-derived neurons became electrically excitable, expressing voltage-dependent TTX-sensitive Na+ channels, low- and high-voltage-activated Ca2+ channels and delayed-rectifier K+ channels. Differentiated cells also possessed functional glutamate, GABA, glycine and purinergic (P2X) receptors. Appearance of voltage-dependent and ligand-gated ion channels appears to be an important early step in the differentiation of NPCs.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Melbourne, Australia : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 28 (2001), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Now that many of the factors and control elements that regulate renin transcription have been identified, the scene is set to address the question of the mode of control.2. Based on current gene control theories, either renin gene transcription in each cell undergoes gradual responses over a continuous range or transcription is switched completely on or completely off. The latter model of ‘binary’ or ‘variegated’ expression fits with observations such as the ‘recruitment’ of new cells for renin expression during strong physiological stimulation and the progressive switching off of expression during development.3. The renin gene offers an excellent general model for testing the mode of control of genes that are subject to continuous modulatory influences from the demands of physiological perturbations. This is because the promoter is well characterized and is subject to the influence of a strong far-upstream enhancer, one of the key elements of the variegation model.4. Renin is also controlled at the post-transcriptional level and this, like transcriptional control, involves cAMP mechanisms. We have cloned the human and mouse homologues of a protein (ZNF265) that is important in renin mRNA processing and stability. This uses ‘zinc fingers’ to bind the mRNA. The role of this and other proteins in splicing and stabilization of mRNA is now being elucidated.5. Unravelling the mechanisms that determine rate of supply of renin mRNA to the biosynthetic machinery is being assisted by advances in concepts and techniques in the rapidly moving field of genomics.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Inbred mouse strains provide the foundation for mouse genetics. By selecting for phenotypic features of interest, inbreeding drives genomic evolution and eliminates individual variation, while fixing certain sets of alleles that are responsible for the trait characteristics of the strain. Mouse ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature genetics 30 (2002), S. 6-7 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Many unicellular organisms are happy haploids for the majority of their life cycle, reverting to a diploid phase only transiently. Haploidy offers distinct advantages to the survival of unicellular species because new variants can be instantly tested, for better or worse, allowing the species to ...
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] To the Editor: With the recent release of the genome-wide sequence for multiple inbred mouse strains, and with resequencing data for a large number of additional strains entering the public domain (http://www.niehs.nih.gov/crg/cprc.htm), we are one step closer to being able to identify the ...
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Embryonic stem cell technology revolutionized biology by providing a means to assess mammalian gene function in vivo. Although it is now routine to generate mice from embryonic stem cells, one of the principal methods used to create mutations, gene targeting, is a cumbersome process. Here we ...
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 293 (1981), S. 447-449 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The Bernal-Fowler-Pauling ice rules1'2 specify that each oxygen is bonded to two of the four hydrogens with which it is coordinated and that there is one hydrogen between each oxygen and its four nearest oxygens. Each hydrogen is bonded to one oxygen and 'hydrogen bonded' to another. With each ...
    Type of Medium: Electronic Resource
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