Autonomic neuroscience

Dr Alexander Gourine
Wellcome Trust Senior Research Fellow
Tel: +44 (0)20 7679 4384
Email: a.gourine@ucl.ac.uk

Lab. Members:

  • Dr Vitaliy Kasymov and
  • Alla Korsak

Collaborators:
Alexander Gourine (MS, PhD) is a Wellcome Trust Senior Research Fellow at University College London. He gained his PhD at the Russian Academy of Medical Sciences (Moscow, Russia), received postdoctoral training in the US and the UK and was appointed to the Department of Physiology as The Wellcome Trust Senior Fellow in 2006. He was awarded the Physiological Society’s Wellcome Trust Prize in the year 2004 for his contribution to understanding the mechanisms underlying chemosensory control of breathing.

Chemosensory control of breathing

We breathe continuously from birth until death to maintain appropriate concentrations of oxygen, CO2 and hydrogen ions (H+) in the blood in various environmental and physiological conditions. Respiratory sensors located in the brain monitor changes in the blood levels of CO2 and H+ and evoke adaptive changes in breathing appropriate to the current metabolic rate and activity. The identity of these respiratory CO2 sensors as yet remains to be determined. The specific molecular mechanisms which transduce changes in blood concentrations of CO2 and H+ into a modified pattern of breathing are also remain elusive. We use a combination of experimental models ranging from cell culture to in vivo animal preparations to identify the nature of the respiratory sensors in the brain and pinpoint the mechanisms which underlie their sensitivity to changes in the levels of CO2 and H+ in the blood.

Research supported by the Wellcome Trust.

Autonomic control in pathological conditions

Beat-by-beat activity of the heart and every single breath are controlled by the central nervous system. Brain mechanisms responsible for regulation of the activity of the cardiovascular and respiratory systems exhibit significant plasticity which ensures survival and adaptation of the organism in changeable environment. In pathological conditions this plasticity may result in adaptive and beneficial modifications in central cardiorespiratory control, but may also lead to maladaptive and detrimental changes when disease is progressing. Surprisingly, very little is known about the mechanisms underlying changes in the activity of brain centres involved in cardiorespiratory control in pathological conditions. In collaboration with Dr Gareth Ackland we investigate neuronal and molecular mechanisms responsible for modifications in the central nervous mechanisms of cardiovascular and respiratory control in different pathological conditions, including heart failure and systemic inflammation leading to sepsis.

Research supported by The Royal Free Peter Samuel Fund and The Intensive Care Society.

Selected publications:

  • Ackland GL, Kasymov V, Gourine AV (2007) Physiological and pathophysiological roles of extracellular ATP in chemosensory control of breathing. Biochem Soc Trans 35:1264-1268.
  • Gourine AV, Dale N, Llaudet E, Poputnikov DM, Spyer KM, Gourine VN (2007) Release of ATP in the central nervous system during systemic inflammation: real-time measurement in the hypothalamus of conscious rabbits. J Physiol 585:305-316.
  • Gourine AV (2005) Wellcome Prize Lecture. On the peripheral and central chemoreception and control of breathing: an emerging role of ATP. J Physiol 568:715-724.
  • Gourine AV, Llaudet E, Dale N, Spyer KM (2005) ATP is a mediator of chemosensory transduction in the central nervous system. Nature 436:108-111.
  • Gourine AV, Llaudet E, Dale N, Spyer KM (2005) Release of ATP in the ventral medulla during hypoxia in rats: role in hypoxic ventilatory response. J Neurosci 25:1211-1218.
  • Gourine AV, Dale N, Gourine VN, Spyer KM (2004) Fever in systemic inflammation: roles of purines. Front Biosci 9:1011-1022.
  • Spyer KM, Dale N, Gourine AV (2004) ATP is a key mediator of central and peripheral chemosensory transduction. Exp Physiol 89:53-59.
  • Gourine AV, Spyer KM (2003) Chemosensitivity of medullary respiratory neurones. A role for ionotropic P2X and GABAA receptors. Adv Exp Med Biol 536:375-387.
  • Gourine AV, Atkinson L, Deuchars J, Spyer KM (2003) Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X2 receptor subunit. J Physiol 552:197-211.
  • Rong W, Gourine AV, Cockayne DA, Xiang Z, Ford AP, Spyer KM, Burnstock G (2003) Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J Neurosci 23:11315-11321.
  • Yao ST, Gourine AV, Spyer KM, Barden JA, Lawrence AJ (2003) Localisation of P2X2 receptor subunit immunoreactivity on nitric oxide synthase expressing neurones in the brain stem and hypothalamus of the rat: a fluorescence immunohistochemical study. Neuroscience 121:411-419.
  • Dale N, Gourine AV, Llaudet E, Bulmer D, Thomas T, Spyer KM (2002) Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real-time measurement in vivo. J Physiol 544:149-160.
  • Gourine AV, Llaudet E, Thomas T, Dale N, Spyer KM (2002) Adenosine release in nucleus tractus solitarii does not appear to mediate hypoxia-induced respiratory depression in rats. J Physiol 544:161-170.
  • Gourine AV, Gourine VN, Tesfaigzi Y, Caluwaerts N, Van LF, Kluger MJ (2002) Role of alpha(2)-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice. Am J Physiol Regul Integr Comp Physiol 283:R218-R226.
  • Gourine AV, Melenchuk EV, Poputnikov DM, Gourine VN, Spyer KM (2002) Involvement of purinergic signalling in central mechanisms of body temperature regulation in rats. Br J Pharmacol 135:2047-2055.