Research interests:

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:

1. What are the precise physiological and molecular mechanisms that underpin the oxygen-sensitivity of the carotid body?
2. 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.

Selected Publications:

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 doi: 10.1016/j.ceca.2007.11.003

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.