P E Light

Summary

Affiliation: University of Alberta
Country: Canada

Publications

  1. pmc Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels
    P E Light
    Departments of Physiology and Biophysics, Pharmacology and Therapeutics, and Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada T2N 4N1
    Proc Natl Acad Sci U S A 97:9058-63. 2000
  2. ncbi request reprint Activation of adenosine triphosphate-sensitive potassium channels by acyl coenzyme A esters involves multiple phosphatidylinositol 4,5-bisphosphate-interacting residues
    Jocelyn E Manning Fox
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Mol Endocrinol 18:679-86. 2004
  3. ncbi request reprint Familial Wolff-Parkinson-White Syndrome: a disease of glycogen storage or ion channel dysfunction?
    Peter E Light
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    J Cardiovasc Electrophysiol 17:S158-S161. 2006
  4. pmc Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel
    Kevin S C Hamming
    Department of Pharmacology, Alberta Diabetes Institute, University of Alberta, Alberta, Canada
    Diabetes 58:2419-24. 2009
  5. pmc Inhibition of beta-cell sodium-calcium exchange enhances glucose-dependent elevations in cytoplasmic calcium and insulin secretion
    Kevin S C Hamming
    Department of Pharmacology, Alberta Diabetes Institute and Cardiovascular Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 59:1686-93. 2010
  6. pmc The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes
    Veronica Lang
    Department of Pharmacology and Alberta Diabetes Institute, Faculty of Medicine and Dentistry, School of Molecular and Systems Medicine, University of Alberta, Edmonton, Alberta, Canada
    Pharmgenomics Pers Med 3:145-61. 2010
  7. doi request reprint Late sodium current inhibition alone with ranolazine is sufficient to reduce ischemia- and cardiac glycoside-induced calcium overload and contractile dysfunction mediated by reverse-mode sodium/calcium exchange
    Daniel Soliman
    Cardiovascular Research Centre, Department of Pharmacology, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1
    J Pharmacol Exp Ther 343:325-32. 2012
  8. ncbi request reprint Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial KATP channels during metabolic inhibition and recovery
    P E Light
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    FASEB J 15:2586-94. 2001
  9. ncbi request reprint Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes
    Peter E Light
    Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    Circulation 107:1962-5. 2003
  10. pmc The ATP-sensitive K(+) channel ABCC8 S1369A type 2 diabetes risk variant increases MgATPase activity
    Mohammad Fatehi
    Alberta Diabetes Institute, Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 61:241-9. 2012

Collaborators

Detail Information

Publications43

  1. pmc Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels
    P E Light
    Departments of Physiology and Biophysics, Pharmacology and Therapeutics, and Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada T2N 4N1
    Proc Natl Acad Sci U S A 97:9058-63. 2000
    ..The high degree of conservation of this site among different K(ATP) channel isoforms suggests that this pathway may have wide significance for the physiological regulation of K(ATP) channels in various tissues and organelles...
  2. ncbi request reprint Activation of adenosine triphosphate-sensitive potassium channels by acyl coenzyme A esters involves multiple phosphatidylinositol 4,5-bisphosphate-interacting residues
    Jocelyn E Manning Fox
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Mol Endocrinol 18:679-86. 2004
    ..2. We propose a model in which these residues mediate both direct electrostatic interactions and allosteric modulations of open state stability...
  3. ncbi request reprint Familial Wolff-Parkinson-White Syndrome: a disease of glycogen storage or ion channel dysfunction?
    Peter E Light
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    J Cardiovasc Electrophysiol 17:S158-S161. 2006
    ..It is the aim of this review to discuss our current knowledge of the cellular disturbances underlying the induction of arrhythmias in patients with PRKAG2 mutations...
  4. pmc Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel
    Kevin S C Hamming
    Department of Pharmacology, Alberta Diabetes Institute, University of Alberta, Alberta, Canada
    Diabetes 58:2419-24. 2009
    ..Furthermore, there have been no studies of the S1369A variant or the combined effect of the two on K(ATP) channel function...
  5. pmc Inhibition of beta-cell sodium-calcium exchange enhances glucose-dependent elevations in cytoplasmic calcium and insulin secretion
    Kevin S C Hamming
    Department of Pharmacology, Alberta Diabetes Institute and Cardiovascular Research Centre, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 59:1686-93. 2010
    ..3 and -1.7 in beta-cells. As pharmacological inhibitors of NCX1 splice variants are in development, the pharmacological profile of beta-cell NCX1.3 and -1.7 and the cellular effects of NCX1 inhibition were investigated...
  6. pmc The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes
    Veronica Lang
    Department of Pharmacology and Alberta Diabetes Institute, Faculty of Medicine and Dentistry, School of Molecular and Systems Medicine, University of Alberta, Edmonton, Alberta, Canada
    Pharmgenomics Pers Med 3:145-61. 2010
    ..SU pharmacogenomics is also discussed with respect to evaluating whether patients with certain K(ATP) channel activation mutations can be successfully switched to SU therapy...
  7. doi request reprint Late sodium current inhibition alone with ranolazine is sufficient to reduce ischemia- and cardiac glycoside-induced calcium overload and contractile dysfunction mediated by reverse-mode sodium/calcium exchange
    Daniel Soliman
    Cardiovascular Research Centre, Department of Pharmacology, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1
    J Pharmacol Exp Ther 343:325-32. 2012
    ..1, we conclude that induction of late INa is upstream of RM NCX1.1 activity and selective inhibition of late INa alone is sufficient to reduce Ca2+i overload and contractile dysfunction in IR injury and cardiac glycoside toxicity...
  8. ncbi request reprint Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial KATP channels during metabolic inhibition and recovery
    P E Light
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    FASEB J 15:2586-94. 2001
    ..Our data suggest that sarc and mitoKATP channel populations play distinct protective roles, triggered by PKC and/or adenosine, during chemically induced hypoxia/reoxygenation...
  9. ncbi request reprint Constitutively active adenosine monophosphate-activated protein kinase regulates voltage-gated sodium channels in ventricular myocytes
    Peter E Light
    Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    Circulation 107:1962-5. 2003
    ..Some PRKAG2 mutations in the human gene encoding for the gamma-subunit of the adenosine monophosphate-activated protein kinase (AMPK) recently have been shown to cause rhythm disturbances (often fatal) in affected patients...
  10. pmc The ATP-sensitive K(+) channel ABCC8 S1369A type 2 diabetes risk variant increases MgATPase activity
    Mohammad Fatehi
    Alberta Diabetes Institute, Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 61:241-9. 2012
    ....
  11. ncbi request reprint Glucagon-like peptide-1 inhibits pancreatic ATP-sensitive potassium channels via a protein kinase A- and ADP-dependent mechanism
    Peter E Light
    Department of Pharmacology Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Mol Endocrinol 16:2135-44. 2002
    ..The marked alteration of the PKA-mediated effects at different ADP levels may provide a cellular mechanism for the glucose-sensitivity of GLP-1...
  12. ncbi request reprint Identification and properties of ATP-sensitive potassium channels in myocytes from rabbit Purkinje fibres
    P E Light
    Department of Physiology and Biophysics, University of Calgary, Alberta, Canada
    Cardiovasc Res 44:356-69. 1999
    ..Our goal was to identify the ATP-sensitive potassium (KATP) channels in cardiac Purkinje cells and to document the functional properties that might distinguish them from KATP channels in other parts of the heart...
  13. pmc Epoxyeicosatrienoic acids protect cardiac cells during starvation by modulating an autophagic response
    V Samokhvalov
    Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
    Cell Death Dis 4:e885. 2013
    ..Thus, we provide new evidence highlighting a central role of the autophagic response in linking EETs with promoting cell survival during deep metabolic stress such as starvation. ..
  14. ncbi request reprint Leptin reduces glucose transport and cellular ATP levels in INS-1 beta-cells
    N T Lam
    Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
    J Mol Endocrinol 32:415-24. 2004
    ..In addition, leptin reduced glucose transport by 35% in isolated rat hepatocytes that also express GLUT2, suggesting that glucose transport may also be altered by leptin in other glucose-responsive tissues such as the liver...
  15. ncbi request reprint Inhibition by protein kinase C of the K(NDP) subtype of vascular smooth muscle ATP-sensitive potassium channel
    W C Cole
    Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada
    Circ Res 87:112-7. 2000
    ..Control of K(NDP) activity by intracellular signaling cascades involving PKC may, therefore, contribute to control of tone and arterial diameter by vasoconstrictors...
  16. pmc Inhibition of matrix metalloproteinases prevents peroxynitrite-induced contractile dysfunction in the isolated cardiac myocyte
    H Leon
    Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada
    Br J Pharmacol 153:676-83. 2008
    ..The purpose of this study was to examine the effects of ONOO(-) on contractile function at the level of the single cardiac myocyte and whether this includes the action of MMPs...
  17. ncbi request reprint Are users of sulphonylureas at the time of an acute coronary syndrome at risk of poorer outcomes?
    J Nagendran
    Division of Cardiac Surgery, Department of Surgery, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada Cardiovascular Research Centre, Faculty of Medicine and Dentistry, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
    Diabetes Obes Metab 15:1022-8. 2013
    ..The purpose of this study is to examine whether patients using K(ATP) channel inhibitors at the time of an acute coronary syndrome are at greater risk of death or heart failure (HF) than those not exposed...
  18. ncbi request reprint Electrophysiological characterization and ionic stoichiometry of the rat brain K(+)-dependent NA(+)/CA(2+) exchanger, NCKX2
    H Dong
    Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada
    J Biol Chem 276:25919-28. 2001
    ....
  19. doi request reprint Variations in tissue selectivity amongst insulin secretagogues: a systematic review
    A S Abdelmoneim
    Faculty of Pharmacy and Pharmaceutical Sciences, 3126 Dentistry Pharmacy Centre, University of Alberta, Edmonton, Alberta, Canada
    Diabetes Obes Metab 14:130-8. 2012
    ..This study was designed to identify insulin secretagogues that selectively bind to SUR1 when given at therapeutic doses...
  20. pmc Inhibition of cardiac voltage-gated sodium channels by grape polyphenols
    C H R Wallace
    Department of Pharmacology, University of Alberta, 9 58 Medical Sciences Building, Edmonton, Alberta, Canada
    Br J Pharmacol 149:657-65. 2006
    ..As polyphenols may also modulate ion channels, and possess structural similarities to several antiarrhythmic VGSC inhibitors, we hypothesised that VGSC inhibition may contribute to cardioprotection by these polyphenols...
  21. ncbi request reprint Cardiac KATP channels and ischemic preconditioning: current perspectives
    P E Light
    University of Calgary, Calgary, Canada
    Can J Cardiol 15:1123-30. 1999
    ..Because KATP channels are rich and varied pharmacologically, it may be possible to target therapeutic agents at the cardiac channel isoform. Such compounds would likely meet the pharmacological criteria for a 'conditioning' agent...
  22. ncbi request reprint The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion
    Patrick E MacDonald
    Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    Diabetes 51:S434-42. 2002
    ..The present article will focus principally on the mechanisms proposed to underlie the glucose dependence of GLP-1's insulinotropic effect...
  23. pmc Protein kinase C modulation of recombinant ATP-sensitive K(+) channels composed of Kir6.1 and/or Kir6.2 expressed with SUR2B
    Kevin S Thorneloe
    Smooth Muscle Research Group and Canadian Institutes of Health Research Group in Regulation of Vascular Contractility, University of Calgary, Calgary, Alberta, Canada
    J Physiol 541:65-80. 2002
    ..1 and their associated SUR2B subunits...
  24. ncbi request reprint Kir6.2 polymorphisms sensitize beta-cell ATP-sensitive potassium channels to activation by acyl CoAs: a possible cellular mechanism for increased susceptibility to type 2 diabetes?
    Michael J Riedel
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    Diabetes 52:2630-5. 2003
    ....
  25. pmc Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt
    Anita Y M Chan
    Cardiovascular Research Group and the Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
    J Biol Chem 283:24194-201. 2008
    ..Taken together, our data suggest that resveratrol exerts anti-hypertrophic effects by activating AMPK via LKB1 and inhibiting Akt, thus suppressing protein synthesis and gene transcription...
  26. doi request reprint Splice variant-dependent regulation of beta-cell sodium-calcium exchange by acyl-coenzyme As
    Kevin S C Hamming
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Mol Endocrinol 22:2293-306. 2008
    ....
  27. ncbi request reprint Experiments to test the role of phosphatidylinositol 4,5-bisphosphate in neurotransmitter-induced M-channel closure in bullfrog sympathetic neurons
    Christopher P Ford
    Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    J Neurosci 23:4931-41. 2003
    ..These are the results that might be expected if agonist-induced activation of PLC and the concomitant depletion of PIP2 contribute to the excitatory action of neurotransmitters that suppress gM...
  28. pmc Resting membrane potential regulates Na(+)-Ca2+ exchange-mediated Ca2+ overload during hypoxia-reoxygenation in rat ventricular myocytes
    István Baczkó
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    J Physiol 550:889-98. 2003
    ..This appears to be due mainly to an effect of diastolic membrane potential on the Na(+)-Ca2+ exchanger, since at depolarized potentials this exchanger mechanism operates in the reverse mode, causing a significant Ca2+ influx...
  29. ncbi request reprint Identification and pharmacological characterization of sarcolemmal ATP-sensitive potassium channels in the murine atrial HL-1 cell line
    Jocelyn E Manning Fox
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    J Cardiovasc Pharmacol 45:30-5. 2005
    ....
  30. ncbi request reprint The phosphatidylinositol 3-kinase inhibitor LY294002 potently blocks K(V) currents via a direct mechanism
    Wasim El-kholy
    Department of Medicine, University of Toronto, Ontario, Canada
    FASEB J 17:720-2. 2003
    ..Furthermore, LY294002 may represent a novel structure from which future Kv channel blockers may be developed...
  31. doi request reprint Elevation in intracellular long-chain acyl-coenzyme A esters lead to reduced beta-cell excitability via activation of adenosine 5'-triphosphate-sensitive potassium channels
    Nicola J Webster
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    Endocrinology 149:3679-87. 2008
    ..These results suggest a direct link between intracellular fatty ester accumulation and K(ATP) channel activation, which may contribute to beta-cell dysfunction in type 2 diabetes...
  32. ncbi request reprint Acyl coenzyme A esters differentially activate cardiac and beta-cell adenosine triphosphate-sensitive potassium channels in a side-chain length-specific manner
    Jocelyn E Manning Fox
    Department of Pharmalology, University of Alberta, Edmonton, Alberta, Canada
    Metabolism 52:1313-9. 2003
    ..We propose that fatty acid metabolism, and the resultant generation of acyl CoAs of varying side-chain length, may be an important regulator of cellular excitability via interactions with the K(ATP) channel...
  33. ncbi request reprint Syntaxin-1A inhibits cardiac KATP channels by its actions on nucleotide binding folds 1 and 2 of sulfonylurea receptor 2A
    Youhou Kang
    Department of Medicine, University of Toronto, Toronto M5S 1A8, Canada
    J Biol Chem 279:47125-31. 2004
    ....
  34. ncbi request reprint Plasma membrane KATP channel-mediated cardioprotection involves posthypoxic reductions in calcium overload and contractile dysfunction: mechanistic insights into cardioplegia
    István Baczkó
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    FASEB J 19:980-2. 2005
    ..We therefore propose that activation of pmKATP channels improves posthypoxic cardiac function via reductions in abnormal diastolic Ca2+ homeostasis mediated by reverse-mode Na+/Ca2+ exchange...
  35. pmc Cardioselectivity of the sulphonylurea HMR 1098: studies on native and recombinant cardiac and pancreatic K(ATP) channels
    Jocelyn E Manning Fox
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    Br J Pharmacol 135:480-8. 2002
    ..The non-aromatic substitutions in the sulphonylurea moiety greatly increase the cardioselectivity of this compound while reducing the overall blocking potency of this sulphonylurea derivative...
  36. pmc Pharmacological activation of plasma-membrane KATP channels reduces reoxygenation-induced Ca(2+) overload in cardiac myocytes via modulation of the diastolic membrane potential
    István Baczkó
    Department of Physiology and Biophysics, University of Calgary, Alberta, Canada
    Br J Pharmacol 141:1059-67. 2004
    ..Hyperpolarization toward normal resting membrane potential favours the Ca(2+) extrusion mode of Na(+)/Ca(2+) exchange...
  37. pmc Metabolic regulation of sodium-calcium exchange by intracellular acyl CoAs
    Michael J Riedel
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada
    EMBO J 25:4605-14. 2006
    ..Additionally, our findings have broad implications for the coupling of Ca(2+) homeostasis to fat metabolism in a variety of tissues...
  38. ncbi request reprint Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts
    Heather Fraser
    CV Therapeutics Inc, Palo Alto, CA 94304, USA
    J Mol Cell Cardiol 41:1031-8. 2006
    ..The beneficial effects of ranolazine in reducing Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion is consistent with the inhibition of late INa mechanism of action...
  39. pmc Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy
    Bernardo V Alvarez
    Department of Physiology, Membrane Protein Research Group, University of Alberta, Edmonton, Canada T6G2H7
    J Physiol 579:127-45. 2007
    ..Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype...
  40. ncbi request reprint Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes
    Michael J Riedel
    Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7
    Hum Genet 116:133-45. 2005
    ....
  41. doi request reprint Upper intestinal lipids trigger a gut-brain-liver axis to regulate glucose production
    Penny Y T Wang
    Toronto General Hospital Research Institute, University Health Network, Toronto M5G 1L7, Canada
    Nature 452:1012-6. 2008
    ..These findings indicate that upper intestinal lipids activate an intestine-brain-liver neural axis to inhibit glucose production, and thereby reveal a previously unappreciated pathway that regulates glucose homeostasis...
  42. ncbi request reprint Saturated and cis/trans unsaturated acyl CoA esters differentially regulate wild-type and polymorphic beta-cell ATP-sensitive K+ channels
    Michael J Riedel
    Department of Pharmacology, University of Alberta, 9 58 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada
    Diabetes 54:2070-9. 2005
    ....
  43. pmc Hypothalamic protein kinase C regulates glucose production
    Rachel Ross
    Departments of Molecular Pharmacology, Medicine, and Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA
    Diabetes 57:2061-5. 2008
    ..2 ATP-sensitive K(+) (K(ATP)) channels inhibit hepatic glucose production. The mechanisms that link the ability of hypothalamic lipid metabolism to the activation of K(ATP) channels remain unknown...