Christopher N Wyatt, PhD
Ph.D., University of Leeds, UK 1994
Early detection of an oxygen deficit in the bloodstream is essential to initiate corrective changes in the breathing pattern of mammals. My research focuses on the critical role in this process of specialized oxygen-sensing organs called the carotid bodies. These tiny neurotransmitter rich organs are located at the bifurcation of the carotid arteries and respond to a fall in blood pO2 and pH with transmitter release. This mechanism evokes an increase in the firing frequency of the carotid sinus nerve which innervates the respiratory centers in the brain and ultimately corrects the pattern of breathing.
The laboratory uses a combination of techniques including electrophysiology, cellular imaging, amperometry, immunocytochemistry and molecular biology to address the following questions:
- What are the precise physiological and molecular mechanisms that underpin the oxygen-sensitivity of the carotid body?
- How do pathological disease states that impact upon respiration alter the physiology of the carotid body? This research specifically addresses the modulation of the carotid body by chronic and chronic intermittent hypoxia.
My recent research has indicated that the energy-sensing enzyme AMP-activated protein kinase is critical in the transduction of hypoxic-signalling by the carotid body. Future research will determine the importance of this enzyme not only in acute hypoxic-signalling but also in the plasticity observed in the carotid body during such disease states as sleep apnea.
Research in the Wyatt laboratory is currently funded by the National Institutes of Health.
Jurcsisn, J. G., Pye, R. L., Ali, J., Barr, B. L & Wyatt, C. N (2015) The CamKKβ inhibitor STO609 causes artifacts in Ca2+ imaging and inhibits BKCa in mouse carotid body type I cells. Adv Exp Med Biol. (accepted)
Ricker, E. M., Pye, R. L., Barr, B. L. & Wyatt, C. N (2015) Selective mu and kappa opioid agonists inhibit voltage-gated Ca2+ entry in isolated neonatal rat carotid body type I cells. Adv Exp Med Biol (accepted)
Pye, R. L., Dunn, E. J., Ricker, E. M., Jurcsisn, J. G., Barr, B. L. & Wyatt, C. N (2015) Acutely administered leptin increases [Ca2+]i and BKCa currents but does not alter chemosensory behaviour in rat carotid body type I cells. Adv Exp Med Biol (accepted)
Carey, E. A., Albers, R. E., Doliboa, S. R., Hughes, M., Wyatt, C. N., Natale, D. R. & Brown, T. L. (2014) AMPK knockdown in placental trophoblast cells results in altered morphology and function. Stem. Cells. Dev. 23 (23), 2921-2930
Evans, A. M., Peers, C., Wyatt, C. N. Kumar, P. & Hardie, D. G. (2012) Ion channel regulation by the LKB1-AMPK signalling pathway: the key to carotid body activation by hypoxia and metabolic homeostasis at the whole body level. Adv Exp Med Biol. 758, 81-90
Shapiro, R. L., Barr, B. L., Putnam, R. W. & Wyatt, C. N. (2012) Acute Hypoxia does not influence intracellular pH in isolated rat carotid body type I cells. Adv Exp Med Biol. 758, 105-107
Tangeman, L., Wyatt, C. N. & Brown, T. L. (2012) Knockdown of AMP-activated protein kinase (AMPK) a1 and a2 catalytic subunits. Journal of RNAi and Gene Silencing. 8, 470-478.
Ross, F. A, Rafferty, J. N., Dallas, M. L., Ogunbayo, O., Ikematsu, N., McClafferty, H., Tian, L., Widmer, H., Rowe, I. C. M., Wyatt, C. N., Shipston, M. J., Peers, C., Hardie, D. G. & Evans, A. M. (2011) Selective expression in carotid body type I cells of a single splice variant of the large conductance calcium- and voltage- activated potassium channel confers regulation by AMP-activated protein kinase. Journal of Biological Chemistry. In Press. DOI: 10.1074/JBC.M110.189779
Thompson, C. M. & Wyatt, C. N. (2011) Inhibition of adenylate cyclase attenuates muscarinic Ca2+ signaling by a PKA-independent mechanism in rat carotid body Type I cells. Respiratory Physiology and Neurobiology. 175, 90-96.
Peers, C., Wyatt, C. N. & Evans, A. M (2010) Mechanisms for acute oxygen sensing in the carotid body.Respiratory Physiology & Neurobiology. 174, 292-298.
Thompson, C. M., Troche, K., Jordan, H. L., Barr, B. L. & Wyatt, C. N. (2010) Evidence for functional, inhibitory, histamine H3 receptors in rat carotid body type I cells. Neuroscience Letters 471, 15-19.
Evans, A. M., Hardie, D. G., Peers, C., Wyatt, C. N., Viollet, B., Kumar, P., Dallas, M. L., Ross, F., Ikematsu, N., Jordan, H. L., Barr, B. L., Rafferty, J. N & Ogunbayo, O (2009). Ion channel regulation by AMPK: The route of hypoxia-response coupling in the carotid body and pulmonary artery. Ann. N.Y. Acad. Sci. 1177, 89-100.
Burlon DC, Jordan HJ, Wyatt CN, (2009). Presynaptic regulation of isolated neonatal rat carotid body type I cells by histamine, Respiratory Physiology & Neurobiology 168 218-223.
Calcraft, P. J., Ruas, M., Pan, Z., Cheng, X., Arredouani, A., Hao, X., Tang, J., Rietdorf, K, Teboul, L., Chuang, K-T., Lin, P., Xiao, R., Wang, C., Zhu, Y., Lin, Y., Wyatt, C. N., Parrington, J., Ma, J., Evans, A. M., Galione, A & Zhu, M. X. (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459, 596-601.
Wyatt, C. N. & Peers, C. (2009). Hetero or homo, hypoxia has them all. J. Physiol (Lond) 587.12, 2717-18.
Wyatt, C. N., Pearson, S. A., Kumar, P., Peers, C., Hardie, D.G. & Evans, A. M. (2008) Key roles for AMP-activated protein kinase in the function of the carotid body? Adv Exp Med Biol. 605, 63-68.
Kinnear, N. P., Wyatt, C. N., Clark, J. H., Calcraft, P.J., Fleischer, S., Jeyakumar, L. H., Nixon, G. F. & Evans, A. M. (2008) Lysosomes co-localize with ryanodine receptor subtype 3 to form a trigger zone for calcium signalling by NAADP in rat pulmonary arterial smooth muscle. Cell Calcium 44, 190-201
Varas R, Wyatt CN, Buckler KJ (2007). Modulation of TASK-like background potassium channels in rat arterial chemoreceptor cells by intracellular ATP and other nucleotides. J. Physiol. 583.2, 521-536.
Peers C, Wyatt CN (2007). The role of maxiK channels in carotid body chemotransduction. Resp. Physiol and Neurobiol. 157, 75-82.
Wyatt CN, Mustard KJW, Pearson SA, Dallas ML, Atkinson L, Kumar P, Peers C, Hardie DG, Evans AM (2007). AMP-activated protein kinase mediates carotid body excitation by hypoxia. J. Biol. Chem. 282 8092-8098.
Wyatt CN, Evans AM (2007). AMP-activated protein kinase and chemotransduction in the carotidbody. Resp. Physiol and Neurobiol. 157, 22-29.
Buckler KJ, Williams BA, Orozco RV, Wyatt CN (2006). The role of TASK-like K+ channels in oxygen sensing in the carotid body. Novartis Found Symp; 272: 73-85.
Evans AM, Mustard KJ, Wyatt CN, Peers C, Dipp M, Kumar P, Kinnear NP, Hardie DG (2005). Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signalling in O2-sensing cells? J Biol Chem; 280(50): 41504-11.
Wyatt CN, Buckler KJ (2004). The effect of mitochondrial inhibitors on membrane currents in isolated neonatal rat carotid body type I cells. J Physiol; 556(Pt1):175-91.
Wyatt CN, Page KM, Berrow NS, Brice NL, Dolphin AC (1998). The effect of overexpression of auxiliary Ca2+ channel subunits on native Ca2+ channel currents in undifferentiated mammalian NG108-15 cells. J Physiol;510(Pt2): 347-60.
Wyatt CN, Peers C (1995). Ca2+-activated K+ channels in isolated type I cells of the neonatal rat carotid body. J Physiol; 483(Pt3): 559-65.
Wyatt CN, Wright C, Bee D, Peers C (1995). O2-sensitive K+ currents in carotid chemoreceptor cells from normoxic and chronically hypoxic rats and their roles in hypoxic chemotransduction. Proc Natl Acad Sci USA;92(1):295-9.