Kenneth Byron, Ph.D.


Professor

Professional Background
B.A., Natural Sciences, 1980
Johns Hopkins University; Baltimore, Maryland

Ph.D., Cell Physiology, 1990
University of Chicago; Chicago, Illinois

Our Research
Signal transduction and regulation of intracellular calcium; mechanisms involved in the generation and regulation of action potentials in vascular smooth muscle cells; ion channel regulation in vascular and airway smooth muscle cells; fluorescence measurements of intracellular ion concentrations, patch clamp electrophysiology, protein biochemistry, image analysis of isolated and in situ blood vessel diameter, precision-cut lung slices, in vivo measurement of blood pressure and flow.

Arterial and airway smooth muscle calcium signaling and ion channel regulation

Research in the Byron lab is broadly related to the cellular and biochemical mechanisms that operate to regulate smooth muscle contraction. Smooth muscle is found in many tissues, including the walls of arteries (vascular smooth muscle) and the airways of the lung (airway smooth muscle). In arteries, the ability of smooth muscle cells to contract or relax allows for moment-to-moment control of artery diameter, and hence determines blood flow and blood pressure. Physiologically, artery diameters reflect a balance of vasoconstrictor or vasodilator influences—in most cases these are circulating or locally released substances that stimulate smooth muscle contraction or relaxation, respectively. A main objective of the research in the Byron laboratory is to elucidate the molecular mechanisms by which vasoactive substances exert their effects, with a long-term goal of identifying improved therapeutic strategies for treatment of cardiovascular diseases.

A significant accomplishment of Dr. Byron’s laboratory has been the identification of 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 calcium (Ca2+) through voltage-sensitive Ca2+ channels in the sarcolemma of the vascular smooth muscle cells. These mechanisms enable the moment-to-moment fine-tuning of vascular tone in response to small changes in AVP concentration in the systemic circulation. The mechanisms identified by the Byron lab are distinct from previously characterized signaling mechanisms, which primarily involve release of intracellular Ca2+ stores and require much higher concentrations of AVP. Higher concentrations of AVP are associated with increased cell growth and cell proliferation. Thus, Dr. Byron’s research has revealed that AVP can control different physiological processes in vascular smooth muscle cells by activating different Ca2+ signaling mechanisms over different ranges of AVP concentration.

The current work of the Byron laboratory focuses on physiological and pharmacological modulation of ion channels in the regulation of smooth muscle tone in arteries (regulating blood flow and blood pressure) and in the airways of the lung (regulating airway constriction). These studies include investigation of off-target effects and novel applications of clinically used drugs in the treatment of cardiovascular and lung diseases. The laboratory utilizes a multifaceted experimental program, including molecular, biochemical, and cell physiological approaches designed to identify the molecules involved in smooth muscle signal transduction. In addition, experiments using isolated tissues and in vivo measurements of cardiovascular and airway function provide a more complete understanding of how these mechanisms are integrated at the organ and whole animal levels.

Select Publications

Byron, K.L. (1996) Vasopressin stimulates Ca2+ spiking activity in A7r5 vascular smooth muscle cells via activation of phospholipase A2.  Circ. Res.  78: 813-820.

Byron, K.L., and Lucchesi, P.A. (2002) Signal transduction of physiological concentrations of vasopressin in A7r5 vascular smooth muscle cells: a role for PYK2 and tyrosine phosphorylation of K+ channels in the stimulation of Ca2+ spiking. J. Biol. Chem. 277: 7298-7307.

Brueggemann, L.I., Markun, D.R., Henderson, K.K., Cribbs, L.L., and Byron, K.L. (2006) Pharmacological and electrophysiological characterization of store-operated currents and capacitative Ca2+ entry in vascular smooth muscle cells. J. Pharmacol. Exp. Ther.  317: 488-499.

Brueggemann, L.I., Moran, C.J., Barakat, J.A., Yeh, J.Z., Cribbs, L.L. and Byron, K.L. (2007) Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 vascular smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 292: H1352-H1363.

Henderson, K.K., and Byron, K.L. (2007) Vasopressin-induced vasoconstriction:  two concentration-dependent signaling pathways. J Appl Physiol. 102: 1402-1409.

Mackie, A.R., Brueggemann, L.I., Henderson, K.K., Shiels, A.J., Cribbs, L.L., Scrogin, K.E., and Byron, K.L. (2008) Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction: Studies in single cells, pressurized arteries and in vivo measurements of mesenteric vascular resistance. J. Pharmacol. Exp. Ther. 325: 475-483.

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

Brueggemann, L.I., Mackie, A.R., Mani, B.K., Cribbs, L.L. & Byron, K.L. (2009). Differential Effects of Selective COX-2 Inhibitors on Vascular Smooth Muscle Ion Channels May Account for Differences in Cardiovascular Risk Profiles. Mol. Pharmacol. 76: 1053-1061.

Mani, B.K., Brueggemann, L.I., Cribbs, L.L., and Byron, K.L. (2011) Activation of vascular KCNQ (Kv7) potassium channels reverses spasmogen-induced constrictor responses in rat basilar artery. Br. J. Pharmacol. 164: 237-249.

Brueggemann, L.I., Kakad, P.P., Love, R.B., Solway, J., Dowell, M.L., Cribbs, L.L., and Byron, K.L.  (2012) Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy. Am J Physiol Lung Cell Mol Physiol 302:L120-L132.

Other Publications