CONTACT INFORMATION http://www.loyola.org
Kenneth Byron
Ph.D.
  • Professor
  • Molecular Pharmacology and Therapeutics
  • Cell and Molecular Physiology
Research Keywords
  • Calcium Channel
  • Cardiovascular System
  • Cerebrovascular Disorders
  • Channelopathies
  • Diabetes
  • Electrophysiology
  • Hypertension
  • Ion Channels
  • Signal Transduction
  • Vascular Biology
Research Summary

Signal transduction and ion channel regulation in vascular smooth muscle

Vascular smooth muscle cells (VSMCs) form a layer of contractile tissue in blood vessel walls. Coordinated contraction or relaxation of these cells determines the vessel diameter and thereby influences blood pressure and the flow of blood through the lumen of the vessel. The contractile state of VSMCs is regulated by the intracellular calcium ion concentration ([Ca2+]i). An increase in [Ca2+]i leads to activation of myosin light chain kinase, myosin phosphorylation, and ultimately to an increase in contraction. Physiologically, an increase in [Ca2+]i may occur in response to circulating or locally released hormones or neurotransmitters that bind to cell surface receptors. Binding is then transduced into an increase in Ca2+ influx across the cell’s outer membrane (sarcolemma) and/or a release of intracellular Ca2+ stores. Hormone-induced Ca2+ signals are important for both VSMC contraction and for initiation of cell proliferation.

Dr. Byron’s laboratory has identified novel signal transduction mechanisms that are activated by physiological concentrations of the vasoconstrictor hormone arginine vasopressin (AVP). A complex cascade of biochemical events is activated when AVP concentrations are increased in the systemic circulation, resulting in phosphorylation of ion channels, changes in membrane voltage, and influx of Ca2+ through voltage-sensitive Ca2+ channels in the sarcolemma. These events are distinct from previously characterized signaling mechanisms, involving release of intracellular Ca2+ stores, that are activated by much higher concentrations of AVP. Higher concentrations of AVP are associated with increased cell growth and proliferation. Thus, Dr. Byron’s research has revealed that AVP can control different physiological processes in VSMCs by activating different Ca2+ signaling mechanisms over different ranges of AVP concentration.

The current work of the laboratory continues to focus on physiological and pharmacological modulation of vascular ion channels in the regulation of vascular tone in health and disease. The laboratory utilizes a multifaceted experimental program, including molecular, biochemical, and cell physiological approaches designed to identify the molecules involved in VSMC signal transduction. In addition, experiments using isolated arterial segments and in vivo measurements of blood flow and blood pressure provide a more complete understanding of how these mechanisms are integrated at the tissue and whole animal levels.

Publications

Differential Activation of Vascular Smooth Muscle Kv7.4, Kv7.5, and Kv7.4/7.5 Channels by ML213 and ICA-069673Brueggemann,L. I.; Haick,J. M.; Cribbs,L. L.; Byron,K. L.Molecular pharmacology 2014 ; ( ):

KCNQ (Kv7) potassium channel activators as bronchodilators: combination with a beta2-adrenergic agonist enhances relaxation of rat airwaysBrueggemann,L. I.; Haick,J. M.; Neuburg,S.; Tate,S.; Randhawa,D.; Cribbs,L. L.; Byron,K. L.American journal of physiology.Lung cellular and molecular physiology 2014 ;306(6):L476-86

Chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate vascular alpha-adrenergic receptor functionBach Iv,H. H.; Wong,Y. M.; Tripathi,A.; Nevins,A. M.; Gamelli,R. L.; Volkman,B. F.; Byron,K. L.; Majetschak,M.Molecular medicine (Cambridge, Mass.) 2014 ; ( ):

Differential Protein Kinase C-Dependent Modulation of Kv7.4 and Kv7.5 Subunits of Vascular Kv7 ChannelsBrueggemann,L. I.; Mackie,A. R.; Cribbs,L. L.; Freda,J.; Tripathi,A.; Majetschak,M.; Byron,K. L.The Journal of biological chemistry 2013 ; ( ):

Social networking among voltage-activated potassium channelsBrueggemann,L. I.; Gentile,S.; Byron,K. L.Progress in molecular biology and translational science 2013 ;117( ):269-302

Blood pressure homeostasis is maintained by a P311-TGF-beta axisBadri,K. R.; Yue,M.; Carretero,O. A.; Aramgam,S. L.; Cao,J.; Sharkady,S.; Kim,G. H.; Taylor,G. A.; Byron,K. L.; Schuger,L.The Journal of clinical investigation 2013 ;123(10):4502-4512

Vascular KCNQ (Kv7) potassium channels as common signaling intermediates and therapeutic targets in cerebral vasospasmMani,B. K.; O'Dowd,J.; Kumar,L.; Brueggemann,L. I.; Ross,M.; Byron,K. L.JOURNAL OF CARDIOVASCULAR PHARMACOLOGY 2013 ;61(1):51-62

Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy.Brueggemann,L. I.; Kakad,P. P.; Love,R. B.; Solway,J.; Dowell,M. L.; Cribbs,L. L.; Byron,K. L.American Journal of Physiology - Lung Cellular & Molecular Physiology 2012 ;302(1):120-132

Exploring arterial smooth muscle Kv7 potassium channel function using patch clamp electrophysiology and pressure myographyBrueggemann,L. I.; Mani,B. K.; Haick,J.; Byron,K. L.Journal of visualized experiments : JoVE 2012 ;(67):e4263. doi(67):e4263

Diclofenac distinguishes among homomeric and heteromeric potassium channels composed of KCNQ4 and KCNQ5 subunits.Brueggemann,L. I.; Mackie,A. R.; Martin,J. L.; Cribbs,L. L.; Byron,K. L.Molecular pharmacology 2011 ;79(1):10-23

Vascular KCNQ channels in humans: the sub-threshold brake that regulates vascular tone?.Mani,B. K.; Byron,K. L.British journal of pharmacology 2011 ;162(1):38-41

Labour pains: giving birth to new mechanisms for the regulation of myometrial contractilityByron,K. L.; Brueggemann,L. I.Journal of Physiology 2009 ;587(Pt 10):2109-2110

Differential effects of selective cyclooxygenase-2 inhibitors on vascular smooth muscle ion channels may account for differences in cardiovascular risk profiles.Brueggemann,L. I.; Mackie,A. R.; Mani,B. K.; Cribbs,L. L.; Byron,K. L.Molecular pharmacology 2009 ;76(5):1053-1061

Opposite regulation of KCNQ5 and TRPC6 channels contributes to vasopressin-stimulated calcium spiking responses in A7r5 vascular smooth muscle cells.Mani,B. K.; Brueggemann,L. I.; Cribbs,L. L.; Byron,K. L.Cell calcium 2009 ;45(4):400-411

Cardiovascular KCNQ (Kv7) potassium channels: physiological regulators and new targets for therapeutic interventionMackie,A. R.; Byron,K. L.Molecular pharmacology 2008 ;74(5):1171-1179

Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction by vasopressin, based on studies in single cells, pressurized arteries, and in vivo measurements of mesenteric vascular resistance.Mackie,A. R.; Brueggemann,L. I.; Henderson,K. K.; Shiels,A. J.; Cribbs,L. L.; Scrogin,K. E.; Byron,K. L.Journal of Pharmacology & Experimental Therapeutics 2008 ;325(2):475-483

Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways.Henderson,K. K.; Byron,K. L.Journal of applied physiology 2007 ;102(4):1402-1409

Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells.Brueggemann,L. I.; Moran,C. J.; Barakat,J. A.; Yeh,J. Z.; Cribbs,L. L.; Byron,K. L.American Journal of Physiology - Heart & Circulatory Physiology 2007 ;292(3):H1352-63

Pharmacological and electrophysiological characterization of store-operated currents and capacitative Ca(2+) entry in vascular smooth muscle cells.Brueggemann,L. I.; Markun,D. R.; Henderson,K. K.; Cribbs,L. L.; Byron,K. L.Journal of Pharmacology & Experimental Therapeutics 2006 ;317(2):488-499

Low voltage-activated calcium channels in vascular smooth muscle: T-type channels and AVP-stimulated calcium spiking.Brueggemann,L. I.; Martin,B. L.; Barakat,J.; Byron,K. L.; Cribbs,L. L.American Journal of Physiology - Heart & Circulatory Physiology 2005 ;288(2):H923-35

Evidence against reciprocal regulation of Ca2+ entry by vasopressin in A7r5 rat aortic smooth-muscle cellsBrueggemann,L. I.; Markun,D. R.; Barakat,J. A.; Chen,H.; Byron,K. L.The Biochemical journal 2005 ;388(Pt 1):237-244

Protein kinase C epsilon-dependent activation of proline-rich tyrosine kinase 2 in neonatal rat ventricular myocytes.Bayer,A. L.; Heidkamp,M. C.; Howes,A. L.; Heller Brown,J.; Byron,K. L.; Samarel,A. M.Journal of Molecular & Cellular Cardiology 2003 ;35(9):1121-1133

Biography

Kenneth L. Byron was born and raised in western Massachusetts, and attended college in Baltimore, Maryland where he earned a B.A. degree in Natural Sciences from Johns Hopkins University. He began his scientific career working for five years as a Laboratory Scientist in the Department of Pharmacology & Toxicology at the University of Maryland in Baltimore until 1985, when he moved to Chicago to pursue a Ph.D. in Cell Physiology. Dr. Byron was awarded the Harry Ginsberg Prize in 1990 from the University of Chicago for his dissertation research on calcium signaling in human fibroblasts. He then spent three years as a Wellcome Trust Fellow at Cambridge University in England, where he continued to investigate calcium signaling mechanisms, but with a focus on vascular smooth muscle. In 1993, Dr. Byron accepted a faculty position at Loyola University Chicago, where he has since established an independent research laboratory that is internationally recognized for its ground-breaking work on the mechanisms of action of vasoconstrictor hormones and the role of ion channels in regulating vascular tone and blood pressure. Dr. Byron is currently a tenured Professor of Molecular Pharmacology and Therapeutics at Loyola University Chicago.