The control of neuronal excitability by potassium channels and neuropeptides

GMSK3spinalcord

Staining of the dorsal horn of the spinal cord with an antibody that specifically identifies subunits of the SK3 calcium-activated potassium channel (KCNN3, KCa2.3). This data, in combination with physiological experiments, identified SK3 as a key protein in controlling the transmission of painful stimuli.

Dr Guy Moss
Reader in Neuroscience
Tel: 020 7679 3752
Email: g.moss@ucl.ac.uk

Lab Members:

  • Dr. David Benton
  • Rosemary Ivanova

Dr Guy Moss graduated with a degree in Physics from Imperial College. He stayed on in the Biophysics group at Imperial to do a Ph.D. studying the molecular mechanisms of general anaesthesia. From there he went to the Department of Pharmacology at Yale University where he was awarded a Donaghue Foundation and James Hudson Brown-Alexander B. Coxe postdoctoral fellowships. In 1996 he joined the faculty at UCL as a lecturer and in 2004 he became a key member of the team running CoMPLEX – UCL’s centre promoting both training and research at the life sciences/physical sciences interface. In 2008 Guy became a Reader in Neuroscience.

We are interested in how neurons function and in this vast area of research our laboratory is focused on a few topics of particular interest. Our work can thus be divided into three main parts. First, we aim to understand the molecular composition, pharmacology and physiological role of potassium channels. We are currently focusing our efforts on calcium-activated potassium channels (channels that open in response to an increase in intracellular calcium). Mammalian genes have been identified for several of these proteins including those producing large, small and intermediate conductance channels. A major challenge in this area is to be able to understand the properties of native channels by studying their cloned counterparts. In order to do this we need to understand the functional effects of alternate splicing in these genes as well as determining regions of the proteins involved in the assembly and pharmacology of both heteromeric and homomeric channel tetramers. We are examining some of these issues by using a combination of techniques including molecular biology, biochemistry, antibody studies, and electrophysiology. Our second interest is in the area of neuropeptide regulation, with a particular emphasis on understanding the processes that regulate peptide release. In this area we have collaborated closely with Matthew Whim’s group at Penn State University and helped to develop a new method for detecting peptide secretion that offers greatly improved temporal resolution. Finally, our third area of interest is in the development and application of new ‘nanobiology’ techniques to help answer important questions in neuroscience. We are particularly interested in scanning ion conductance microscopy and collaborate with groups both at Imperial and Cambridge in the application of this technique.

GMMatthewproject2

Images from Matthew Caldwell’s CoMPLEX summer project in the laboratory. This simulation illustrates image reconstruction using patterned illumination - a technique that is increasingly important in bio-imaging. A) The original image containing fine structure, some of which is simulated so as to be below the microscope resolution. B) Simulation of what would normally be seen of the image (‘distorted’ by the microscope point-spread function and ‘out of focus’ light). C) Simulation of a structured light image, one of several used in the final reconstruction shown in D. D) Improved, reconstructed image - note the ‘edge enhancement and reduced blurring. Although some artefacts are also introduced during this reconstructions these can be partially eliminated by subsequent processing.

Full publication list with PDFs

Selected Publications:

  • Ian C. Duguid, Yuriy Pankratov, Guy W. J. Moss, and Trevor G. Smart (2007). Somatodendritic Release of Glutamate Regulates Synaptic Inhibition in Cerebellar Purkinje Cells via Autocrine mGluR1 Activation. J. Neurosci.; 27, 12464-12474.
  • Siu SC, Boushaba R, Topoyassakul V, Graham A, Choudhury S, Moss G, Titchener-Hooker N.J. (2006). Visualising fouling of a chromatographic matrix using confocal scanning laser microscopy. Biotechnol Bioeng., Jun. 30.
  • Parmvir K. Bahia, Rie Suzuki, David C. H. Benton, Amanda J. Jowett, Mao Xiang Chen, Derek. J. Trezise, Anthony H. Dickenson, and Guy W. J. Moss (2005). A Functional Role for Small-Conductance Calcium-Activated Potassium Channels in Sensory Pathways Including Nociceptive Processes. Journal of Neuroscience 25: 3489-3498;
  • Matthew D. Whim and Guy W. J. Moss (2004). FMRFamide tagging—how an ionotropic receptor can be used to measure peptide secretion. Methods, 33(4), 295-301
  • Matthew D. Whim and Guy W. J. Moss (2004). Measurement of neuropeptide release and dense core granule fusion. Methods, 33(4), 265-6.
  • Alan S. Monaghan David C.H. Benton, Parmvir K. Bahia, Ramine Hosseini, Yousaf A. Shah, Dennis G. Haylett & Guy W.J. Moss. (2004). The SK3 subunit of small conductance Ca2+-activated K+ channels interacts with both SK1 and SK2 subunits in a heterologous expression system. Journal of Biological Chemistry, 279, 1003-1009.
  • David C.H. Benton, Alan S. Monaghan, Ramine Hosseini, Parmvir K. Bahia, Dennis G. Haylett and Guy W.J. Moss. (2003). Small conductance Ca2+-activated K+ channels formed by the expression of rat SK1 and SK2 genes in HEK 293 cells. Journal of Physiology, Vol. 553: 3-11.
  • Julia Gorelik, Yuchun Gu, Hilmar A. Spohr, Andrew I. Shevchuk, Max J. Lab, Sian E. Harding, Christopher R. W. Edwards, Michael Whitaker, Guy W. J. Moss, David C. H. Benton, Daniel Sánchez, Alberto Darszon, Igor Vodyanoy, David Klenerman, and Yuri E. Korchev (2002) Ion Channels in Small Cells and Subcellular Structures Can Be Studied with a Smart Patch-Clamp System. Biophys. J., Vol. 83: 3296-3303.
  • Matthew D. Whim, and Moss, Guy W. J., (2001). A novel technique that measures peptide secretion on a millisecond timescale reveals rapid changes in release. Neuron, 30, p.37-50.
  • Hosseini Ramine, David C.H. Benton, Philip M. Dunn, Donald H. Jenkinson and Guy W.J. Moss, (2001). SK3 is an important component of K+ channels mediating the afterhyperpolarization in cultured rat SCG neurones. Journal of Physiology, Vol. 535.2, 323-334.