Prof David Brown
Principal Research Fellow
Neuro, Physiology & Pharmacology
Div of Biosciences
- Joined UCL
- 15th Oct 2004
Many neurotransmitters in the brain target receptors that couple to G proteins (G protein-coupled receptors, or GPCRs) and alter nerve cell activity indirectly by modifying the function of endogenous ion channels in the nerve cell membrane. We are interested in the mechanisms whereby GPCRs regulate ion channel activity and the consequences this has for nerve cell activity. Much of our work is directed toward studying the regulation of Kv7 potassium channels. This is a small (5-member) family of potassium channel subunits which are strikingly prone to spontaneous mutations that generate human cardiac and neural disorders. Four of these subunits (Kv7.2 to 7.5) are present in nerve cells and constitute a long-established potassium channel known as the M-channelâ (see Brown Adams, 1980: Nature, 283, 673-676). These channels are closed by activating GPCRs that couple to the Gq class of G-proteins (for example, M1 and M3 muscarinic acetylcholine receptors (mAChRs), or groups 1 and 5 metabotropic glutamate receptors), with a consequential increase in neural excitability. Channel closure through M1 mAChR activation results from membrane phosphatidyl-4,5-bisphosphate (PIP2) hydrolysis and consequent depletion of PIP2 (since the channels require PIP2 to open (see Delmas Brown, 2005: Nat.Revs. Neurosci., 2005: 6, 850-862). We have been studying the gating and molecular targetting of Kv7 channels by PIP2 (see Telezhkin et al, 2013:.J Gen Physiol 140:41-53; Pflugers Arch. 465:945-953).
A kinetic model for PIP2 gating of M-type Kv7 channels can be seen at: https://www.ucl.ac.uk/biosciences/departments/npp/people/dab/kcnq-kinetic-model
· Dr. Steve Marsh
· Dr. Alexander K. Filippov (Honorary Research Associate)
· Dr. Vselovod Telezhkin (Visiting Research Associate)
Deceased lab members.
Dr. James Halliwell. James was a much-valued member of our laboratories from 1968 to 1971 and from 1978 to 1990, and continued to share labs with us from 2003 until his death on March 7th 2012. His obituary, with recollections by some of his colleagues, may be seen on the Physiological Society’s website at http://www.physoc.org/obituary-notices (search 2012).
Dr. Alexander Selyanko. Alex was another highly-respected and long-standing member of our laboratory from 1983-4 and from1991until his death on September 23rd, 2001. His obituary is on pages 33-34 in the Spring 2002 issue of Physiology News at http://www.physoc.org/magazine
- St Bartholomews Hospital
- PhD, Pharmacology | 1961
BiographyProfessor David A. Brown FIBiol, FRS joined the department in April 1987 and served as Head of Department from October 1987 to April 2002. He graduated from University College with a BSc degree in Chemistry, Zoology and Physiology, followed by Special Physiology, and from St Bartholomew's Hospital Medical College with a PhD in Pharmacology. Prior to coming to UCL he was Wellcome Professor of Pharmacology at the School of Pharmacy. He has also held visiting professorships in the Universities of Chicago, Iowa and Texas, and the University of Kanazawa (Japan), and has been a Fogarty Scholar-in-Residence at the National Institutes of Health in the United States. He was elected FRS in 1990 and was awarded the Feldberg Prize in 1992. He is past editor-in-chief of the British Journal of Pharmacology, and has served on the editorial boards of many other journals, including the Journal of Physiology, Neuron, Trends in Neuroscience and Proceedings of the Royal Society.
Symposium. In July 2013 a Symposium on Ion Channel Regulation and Neuronal Physiology, organized by Dr. Mala M. Shah (UCL SoP) and Professor Trevor Smart (UCL,NPP), and sponsored by the Physiological and British Pharmacological Societies, was held at the Royal Society to celebrate David Brown’s research career. A report of this meeting in Physiology News (Winter 2013, page 17) can be viewed at http://www.physoc.org/magazine