Keith Buckler

I lecture and give tutorials on ‘Physiology and Pharmacology’ for the first-year Medicine courses; ‘Applied Physiology and Pharmacology’ for the second-year Medicine course, and ‘Body and Cells’ for the first-year Biomedical Sciences course. I also give lectures and tutorials in two Final Honour School (FHS) options: ‘Cardiovascular Science’ and ‘Endocrinology & Metabolism’.

I teach first-year students, in groups of two or three, throughout the year (typically five tutorials per term). Teaching of second-year medical students is conducted in a similar manner but only over the first two terms (the 1st BM Part 2 examination is at the beginning of the third term).

Together with Paul Fairchild and Anna Hoerder-Suabedissen I also provide general tutorial support to FHS students (second & third year) depending on their choice of options. Highly specialised tutorial support for the FHS themes is organised centrally via an exchange scheme between colleges. Under this scheme I provide tutorials for students from any college studying selected themes.

I also supervise undergraduate research projects and extended essays, all of which are key parts of the final-year course. In addition to undergraduate teaching I supervise graduate research students studying for DPhils.

My research focusses mainly upon the mechanisms of acute oxygen-sensing in arterial chemoreceptors. These organs are vital to the control of breathing in that they measure blood levels of oxygen, carbon dioxide and pH (acidity). This information is then relayed to the brainstem which elicits compensatory changes in breathing, cardiac output and blood flow. For example, even brief exposure to a low oxygen environment results in a reflex increase in breathing within a minute. In addition to their physiological role in the homeostatic control of breathing and the cardiovascular system, they have also been implicated in maladaptive/pathological events including sleep apnea and some forms of neurogenic hypertension.

My work is primarily focussed upon understanding how the sensory (type-1) cells of the carotid body detect hypoxia. This research is mainly conducted at the cellular level and involves the study of calcium signaling, electrical signaling, the regulation of a particular class of potassium channel (TASK channels) and the role of mitochondria as oxygen-sensors.

I am also interested in the role chemoreceptor plasticity plays in adaptation to prolonged periods of hypoxia, for example during acclimatisation to altitude. In collaboration with Peter Ratcliffe’s group (Nuffield Department of Medicine) we are investigating the role of the HIF (hypoxia inducible factor) signaling system in enhancing chemoreceptor sensitivity to acute hypoxia.

I also study the effects of anaesthetics on chemoreception. Many general anaesthetics suppress breathing and inhibit ventilatory responses to hypoxia (this can be problematic in the post-operative period). In collaboration with Jaideep Pandit (Nuffield Department of Clinical Neurosciences) I have found that some anaesthetics inhibit chemoreceptor responses to hypoxia by activating TASK potassium channels. We are currently trying to understand of how this works and to investigate the possible use of TASK channel inhibitors as ventilatory stimulants to counteract these unwanted side effects of anaesthetics.

Review

Buckler, Keith (2015), ‘TASK channels in arterial chemoreceptors and their role in oxygen and acid sensing’, Pflugers Archiv : European journal of physiology 467: 10, 1007/s00424-015-1689-1

Other Publications

O’Donohoe, P., Huskens, N., Turner, P., Pandit, J., Buckler, K., ‘A1899, PK-THPP, ML365, and Doxapram inhibit endogenous TASK channels and excite calcium signaling in carotid body type-1 cells’, Physiological Reports 6 (2018), e13876. 10.14814/phy2.13876

Fielding, J., Hodson, E., Cheng, X., Ferguson, D., Eckardt, L., Adam, J., Lip, P., Maton‐Howarth, M., Ratnayaka, I., Pugh, C., Buckler, K., Ratcliffe, P., Bishop, T., ‘PHD2 inactivation in Type I cells drives HIF‐2α dependent multi‐lineage hyperplasia and the formation of paraganglioma‐like carotid bodies’, The Journal of Physiology 596 (2018), 10.1113/jp275996

Hodson, E., Nicholls, L., Turner, P., Llyr, R., Fielding, J., Douglas, G., Ratnayaka, I., Robbins, P., Pugh, C., Buckler, K., Ratcliffe, P., Bishop, T., ‘Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF-2 pathway’, The Journal of Physiology 594 (2015), 10.1113/JP271050

Turner P.J., Buckler K.J., ‘Oxygen and mitochondrial inhibitors modulate both monomeric and heteromeric TASK-1 and TASK-3 channels in mouse carotid body type-1 cells’, The Journal of Physiology 591(Pt 23) (2013), 5977-98

Buckler K.J., Turner P.J. (2013) ‘Oxygen sensitivity of mitochondrial function in rat arterial chemoreceptor cells’, The Journal of Physiology 591(Pt 14) (2013), 3549-63