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Lily Yeh Jan - One of the best experts on this subject based on the ideXlab platform.

  • targeting Potassium Channels in cancer
    Journal of Cell Biology, 2014
    Co-Authors: Xi Huang, Lily Yeh Jan
    Abstract:

    Potassium Channels are pore-forming transmembrane proteins that regulate a multitude of biological processes by controlling Potassium flow across cell membranes. Aberrant Potassium channel functions contribute to diseases such as epilepsy, cardiac arrhythmia, and neuromuscular symptoms collectively known as channelopathies. Increasing evidence suggests that cancer constitutes another category of channelopathies associated with dysregulated channel expression. Indeed, Potassium channel–modulating agents have demonstrated antitumor efficacy. Potassium Channels regulate cancer cell behaviors such as proliferation and migration through both canonical ion permeation–dependent and noncanonical ion permeation–independent functions. Given their cell surface localization and well-known pharmacology, pharmacological strategies to target Potassium channel could prove to be promising cancer therapeutics.

  • er transport signals and trafficking of Potassium Channels and receptors
    Current Opinion in Neurobiology, 2002
    Co-Authors: Lily Yeh Jan
    Abstract:

    Channels and receptors on the cell surface mediate neuronal signaling. It is therefore important to understand how their surface density is controlled. Recent studies on the trafficking of Potassium Channels and neurotransmitter receptors have revealed unexpected complexity in the regulation of transport from the endoplasmic reticulum to the Golgi apparatus, raising the possibility that the surface composition of Channels and receptors may be adjusted by controlling their export from the endoplasmic reticulum.

  • cloned Potassium Channels from eukaryotes and prokaryotes
    Annual Review of Neuroscience, 1997
    Co-Authors: Lily Yeh Jan, Yuh Nung Jan
    Abstract:

    Potassium Channels contribute to the excitability of neurons and signaling in the nervous system. They arise from multiple gene families including one for voltagegated Potassium Channels and one for inwardly rectifying Potassium Channels. Features of Potassium permeation, channel gating and regulation, and subunit interaction have been analyzed. Potassium Channels of similar design have been found in animals ranging from jellyfish to humans, as well as in plants, yeast, and bacteria. Structural similarities are evident for the pore-forming subunits and for the subunits, which could potentially regulate channel activity according to the level of energy and/or reducing power of the cell.

  • cloned Potassium Channels from eukaryotes and prokaryotes
    Annual Review of Neuroscience, 1997
    Co-Authors: Lily Yeh Jan, Yuh Nung Jan
    Abstract:

    Potassium Channels contribute to the excitability of neurons and signaling in the nervous system. They arise from multiple gene families including one for voltage-gated Potassium Channels and one for inwardly rectifying Potassium Channels. Features of Potassium permeation, channel gating and regulation, and subunit interaction have been analyzed. Potassium Channels of similar design have been found in animals ranging from jellyfish to humans, as well as in plants, yeast, and bacteria. Structural similarities are evident for the pore-forming alpha subunits and for the beta subunits, which could potentially regulate channel activity according to the level of energy and/or reducing power of the cell.

  • Potassium Channels and their evolving gates
    Nature, 1994
    Co-Authors: Lily Yeh Jan, Yuh Nung Jan
    Abstract:

    Potassium Channels allow Potassium ions to flow across the membrane and play a key role in maintaining membrane potential. Recent research has begun to reveal how these Channels transport Potassium in preference to other ions, how their activity is controlled, and how they are related to other Channels.

Duxin Qing - One of the best experts on this subject based on the ideXlab platform.

  • tanshinone iia elicited vasodilation in rat coronary arteriole roles of nitric oxide and Potassium Channels
    European Journal of Pharmacology, 2009
    Co-Authors: Guobao Wu, Enxiang Zhou, Duxin Qing
    Abstract:

    Abstract Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA, the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of tanshinone IIA on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone IIA-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of tanshinone IIA, the roles of endothelium, endothelium-derived vasoactive factors and Potassium Channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca2+)-activated Potassium Channels (BKca) significantly decreased the vasodilation elicited by Tanshinone IIA. The results indicated that tanshinone IIA induces an endothelium-dependent vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the vasodilation; activation of BKca Channels plays an important role in the vasodilation.

  • tanshinone iia elicited vasodilation in rat coronary arteriole roles of nitric oxide and Potassium Channels
    European Journal of Pharmacology, 2009
    Co-Authors: Guobao Wu, Enxiang Zhou, Duxin Qing
    Abstract:

    Abstract Salvia miltiorrhiza has been widely used in the treatment of various cardiovascular diseases due to its ability to improve coronary microcirculation and increase coronary blood flow. Tanshinone IIA, the major active lipophilic ingredient responsible for the beneficial actions of Salvia miltiorrhiza, was shown to induce vasodilation in coronary arteries. But its effects on coronary arterioles remain unknown. The purpose of this study was to investigate the effects of tanshinone IIA on isolated rat coronary arteriole and the underlying mechanisms. Coronary arterioles were carefully dissected, cannulated and pressurized. Tanshinone IIA-elicited vascular inner diameter change was recorded by a computerized diameter tracking system. To investigate the mechanisms governing the vasodilative effects of tanshinone IIA, the roles of endothelium, endothelium-derived vasoactive factors and Potassium Channels were assessed respectively. Endothelium denudation, inhibition of nitric oxide synthase (NOS), inhibition of the cytochrome P450 epoxygenase, and blockade of the large conductance calcium(Ca2+)-activated Potassium Channels (BKca) significantly decreased the vasodilation elicited by Tanshinone IIA. The results indicated that tanshinone IIA induces an endothelium-dependent vasodilation in coronary arterioles; nitric oxide (NO) and cytochrome P450 metabolites contribute to the vasodilation; activation of BKca Channels plays an important role in the vasodilation.

Maurizio Taglialatela - One of the best experts on this subject based on the ideXlab platform.

  • vasorelaxation by hydrogen sulphide involves activation of kv7 Potassium Channels
    Pharmacological Research, 2013
    Co-Authors: Alma Martelli, Lara Testai, Maria Cristina Breschi, Francesco Miceli, Maurizio Taglialatela, Kim Lawson, Nc Mckay, Vincenzo Calderone
    Abstract:

    Hydrogen sulphide (H2S) has been recently hypothesized to be an endogenous adipocyte-derived relaxing factor, evoking vasorelaxation of conductance and resistance vessels. Although the activation of ATP-sensitive Potassium Channels is known to play a central role in H2S-induced vasorelaxation, activation of vascular Kv7 voltage-gated Potassium Channels has also been suggested. To investigate this possibility, the ability of selective activators and blockers of distinct classes of Potassium Channels to affect vasodilation induced by the H2S-donor NaHS, as well as NaHS-induced Rb(+) efflux in endothelium-denuded rat aortic rings, was investigated. NaHS-induced changes of membrane potential were fluorimetrically assessed on human vascular smooth muscle (VSM) cells. Modulation of Kv7.4 Channels by NaHS was assessed by electrophysiological studies, upon their heterologous expression in CHO cells. In isolated aortic rings, NaHS evoked vasorelaxing responses associated with an increase of Rb(+)-efflux. NaHS promoted membrane hyperpolarization of human VSM cells. These effects were antagonized by selective blockers of Kv7 Channels. The H2S-donor caused a left-shift of current activation threshold of Kv7.4 Channels expressed in CHO cells. Altogether, these results suggest that the activation of Kv7.4 Channels is a key mechanism in the vascular effects of H2S. Given the relevant roles played by Kv7.4 Channels in VSM contractility and by H2S in circulatory homeostasis regulation, these findings provide interesting insights to improve our understanding of H2S pathophysiology and to focus on Kv7.4 Channels as novel targets for therapeutic approaches via the "H2S-system".

  • driving with no brakes molecular pathophysiology of kv7 Potassium Channels
    Physiology, 2011
    Co-Authors: Maria Virginia Soldovieri, Francesco Miceli, Maurizio Taglialatela
    Abstract:

    This review describes the molecular architecture, physiological role, and involvement in genetically determined channelopathies of Kv7 Potassium Channels and highlights their relevance as targets for pharmacological treatment of several human disorders.

Yuh Nung Jan - One of the best experts on this subject based on the ideXlab platform.

  • cloned Potassium Channels from eukaryotes and prokaryotes
    Annual Review of Neuroscience, 1997
    Co-Authors: Lily Yeh Jan, Yuh Nung Jan
    Abstract:

    Potassium Channels contribute to the excitability of neurons and signaling in the nervous system. They arise from multiple gene families including one for voltagegated Potassium Channels and one for inwardly rectifying Potassium Channels. Features of Potassium permeation, channel gating and regulation, and subunit interaction have been analyzed. Potassium Channels of similar design have been found in animals ranging from jellyfish to humans, as well as in plants, yeast, and bacteria. Structural similarities are evident for the pore-forming subunits and for the subunits, which could potentially regulate channel activity according to the level of energy and/or reducing power of the cell.

  • cloned Potassium Channels from eukaryotes and prokaryotes
    Annual Review of Neuroscience, 1997
    Co-Authors: Lily Yeh Jan, Yuh Nung Jan
    Abstract:

    Potassium Channels contribute to the excitability of neurons and signaling in the nervous system. They arise from multiple gene families including one for voltage-gated Potassium Channels and one for inwardly rectifying Potassium Channels. Features of Potassium permeation, channel gating and regulation, and subunit interaction have been analyzed. Potassium Channels of similar design have been found in animals ranging from jellyfish to humans, as well as in plants, yeast, and bacteria. Structural similarities are evident for the pore-forming alpha subunits and for the beta subunits, which could potentially regulate channel activity according to the level of energy and/or reducing power of the cell.

  • Potassium Channels and their evolving gates
    Nature, 1994
    Co-Authors: Lily Yeh Jan, Yuh Nung Jan
    Abstract:

    Potassium Channels allow Potassium ions to flow across the membrane and play a key role in maintaining membrane potential. Recent research has begun to reveal how these Channels transport Potassium in preference to other ions, how their activity is controlled, and how they are related to other Channels.

John P Adelman - One of the best experts on this subject based on the ideXlab platform.

  • international union of pharmacology xli compendium of voltage gated ion Channels Potassium Channels
    Pharmacological Reviews, 2003
    Co-Authors: George A Gutman, John P Adelman, George K Chandy, Jayashree Aiyar, Douglas A Bayliss, David E Clapham, Manuel Covarriubias, Gary V Desir, Kiyoshi Furuichi, Barry Ganetzky
    Abstract:

    This summary article presents an overview of the molecular relationships among the voltage-gated Potassium Channels and a standard nomenclature for them, which is derived from the IUPHAR Compendium of Voltage-Gated Ion Channels.1 The complete Compendium, including data tables for each member of the Potassium channel family can be found at http://www.iuphar-db.org/iuphar-ic/.

  • Calcium-activated Potassium Channels.
    Current Opinion in Neurobiology, 1998
    Co-Authors: Cecilia Vergara, Ramon Latorre, Neil V. Marrion, John P Adelman
    Abstract:

    Calcium-activated Potassium Channels are fundamental regulators of neuronal excitability, participating in interspike interval and spike-frequency adaptation. For large-conductance calcium-activated Potassium (BK) Channels, recent experiments have illuminated the fundamental biophysical mechanisms of gating, demonstrating that BK Channels are voltage gated and calcium modulated. Structurally, BK Channels have been shown to possess an extracellular amino-terminal domain, different from other Potassium Channels. Domains and residues involved in calcium-gating, and perhaps calcium binding itself, have been identified. For small- and intermediate-conductance calcium-activated Potassium Channels, SK and IK Channels, clones have only recently become available, and they show that SK Channels are a distinct subfamily of Potassium Channels. The biophysical properties of SK Channels demonstrate that kinetic differences between apamin-sensitive and apamin-insensitive slow afterhyperpolarizations are not attributable to intrinsic gating differences between the two subtypes. Interestingly, SK and IK Channels may prove effective drug targets for diseases such as myotonic muscular dystrophy and sickle cell anemia.

  • determinants of apamin and d tubocurarine block in sk Potassium Channels
    Journal of Biological Chemistry, 1997
    Co-Authors: Takahiro M. Ishii, James Maylie, John P Adelman
    Abstract:

    Abstract Small conductance calcium-activated Potassium Channels show a distinct pharmacology. Some, but not all, are blocked by the peptide toxin apamin, and apamin-sensitive Channels are also blocked by d-tubocurarine. Cloned SK Channels (small conductance calcium-activated Potassium channel) recapitulate these properties. We have investigated the structural basis for these differences and found that two amino acid residues on either side of the deep pore are the primary determinants of sensitivity to apamin and differential block by d-tubocurarine. Therefore, the pharmacology of SK Channels compared with other Potassium Channels correlates with structural differences in the outer pore region. However, introduction of a tyrosine residue in the position analogous to that which determines sensitivity to external tetraethylammonium for voltage-gated Potassium Channels endows SK Channels with an equivalent tetraethylammonium sensitivity, indicating that the outer vestibules of the pores are similar. The pharmacology of Channels formed in oocytes coinjected with SK1 and SK2 mRNAs, or with SK1-SK2 dimer mRNA, show that SK subunits may form heteromeric Channels.

  • small conductance calcium activated Potassium Channels from mammalian brain
    Science, 1996
    Co-Authors: M Kohler, James Maylie, Neil V. Marrion, Birgit Hirschberg, Chris T Bond, J M Kinzie, John P Adelman
    Abstract:

    Members of a previously unidentified family of Potassium channel subunits were cloned from rat and human brain. The messenger RNAs encoding these subunits were widely expressed in brain with distinct yet overlapping patterns, as well as in several peripheral tissues. Expression of the messenger RNAs in Xenopus oocytes resulted in calcium-activated, voltage-independent Potassium Channels. The Channels that formed from the various subunits displayed differential sensitivity to apamin and tubocurare. The distribution, function, and pharmacology of these Channels are consistent with the SK class of small-conductance, calcium-activated Potassium Channels, which contribute to the afterhyperpolarization in central neurons and other cell types.

  • Calcium-activated Potassium Channels expressed from cloned complementary DNAs
    Neuron, 1992
    Co-Authors: John P Adelman, Chris T Bond, Ke-zhong Shen, Michael P. Kavanaugh, Robin A. Warren, Yan-na Wu, A. Lagrutta, R. Alan North
    Abstract:

    Abstract Calcium-activated Potassium Channels were expressed in Xenopus oocytes by injection of RNA transcribed in vitro from complementary DNAs derived from the slo locus of Drosophila melanogaster. Many cDNAs were found that encode closely related proteinsof about 1200 aa. The predicted sequences of these proteins differ by the substitution of blocks of amino acids at five identified positions within the putative intracellular region between residues 327 and 797. Excised inside-out membrane patches showed Potassium channel openings only with micromolar calcium present at the cytoplasmic side; activity increased steeply both with depolarization and with increasing calcium concentration. The single-channel conductance was 126 pS with symmetrical Potassium concentrations. The mean open time of the Channels was clearly different for Channels having different subsituent blocks of amino acids. The results suggest that alternative splicing gives rise to a large family of functionally diverse, calcium-activated Potassium Channels.