Department of Neuroscience, Cell Biology, & Anatomy
Room 2.202 Basic Science Building
: 1069 |
409-772-5464 | Fax:
(409) 772-3381 | firstname.lastname@example.org
Education and Training
PhD, University New South Wales, Sydney, Australia
Post-Doctoral, University of New South Wales, Sydney Australia
Post-Doctoral, Max Planck Institute Gattingen, West Germany
BS, Monash University, Melbourne, Australia
The mammalian brain is a mechanosensitive (MS) organ that responds to different mechanical forces ranging from intrinsic forces implicated in brain morphogenesis to extrinsic forces that can cause concussion and traumatic brain injury. However, little is known of the mechanosensors that transduce these forces. We have used cell-attached patch clamp recording to measure single MS channel currents and their effects on spike activity in identified mouse brain neurons. We find that both neocortical and hippocampal pyramidal neurons express MS cation channels, and most significantly, single channel currents can trigger spiking in these neurons (Fig.1). In a continuing effort, we are interested in identifying the MS molecules expressed in the brain and their physiological and pathological roles.
We are also interested in the concept that the mechanical forces that develop within a proliferating tumor actually plays a role in modulating cancer progression. In particular, we have identified a specific MS membrane ion channel in human prostate tumor cells that transduces intrinsic mechanical forces into Ca2+ influx and in this way regulates prostate tumor cell migration and invasion. Furthermore, the gating mode of the channel displays plasticity with motile and nonmotile tumor cells showing different gating modes. Most significantly external mechanical forces can switch gating from a "nonmotile" to a "motile" gating mode. Our current research efforts are focused on identifying the specific molecular mechanisms that underlie this mechanosensory switch in channel gating.
Zhang, Y., Gao, F., Popov, V., Wan, J. and Hamill, O.P. Mechanically-gated channel activity in cytoskeleton
deficient blebs and vesicles from
Xenopus oocytes. J. Physiol.
523.1: 117-129, 2000.
Maroto, R. and Hamill, O.P. Brefeldin A block of
integrin-dependent mechanosensitive ATP release from
Xenopus oocytes reveals a novel mechanism of
mechanotransduction. J.Biol.Chem. 276: 23867-23872,
Hamill, O.P. and Martinac, B.A Molecular
Basis of Mechanotransduction in Living Cells.
Physiol. Revs. 81: 685-740, 2001.
Martinac, B. and Hamill, O.P.. Gramicidin channels
switch between stretch activation and stretch
inactivation depending upon bilayer thickness Proc.
Natl. Acad. Sci. USA, 99: 4308-4312, 2002.
Hamill, O.P. and
Maroto, R. TRPCs as MS channels. Current Topics
in Membrane Transport. 59; 191-23, 2007.
Maroto, R. and Hamill, O.P. MscCa regulation of
tumor cell migration and metastastis. Current
Topics in Membrane Transport. 485-509,
Hurricane Ike!! 2008
Maroto R., Kurosky, A. and Hamill, O.P. Mechanosensitive channels in human prostate tumor cells. Channels. 6: 290-307, 2012
Soria B., Navas, S., Hmadcha, A.and Hamill, O.P. Single Mechanosensitive and Ca2+-Sensitive Channel Currents Recorded from Mouse and Human Embryonic Stem Cells. J. Memb Biology. 2012: 246; 215-230, 2013.
Hamill, O.P., Patch Clamp technique. Encyclopedia of life Sciences. John Wiley & Sons, Ltd. Chichester. pp.1-14, 2014.
Nikolaev, Y.A., Dosen, P.J., Laver, D.R., van Helde, D.F. and Hamill, O.P. Single mechanically-gated cation channel currents can trigger action potentials in neocortical and hippocampal pyramidal neurons. Brain Res. 1608, 1-13, 2015.
Nikolaev, Y.A., Dosen, P.J., Laver, D.R., van Helden, D.F. and Hamill, O.P. Biophysical factors that promote mechanically-induced action potentials in neocortical and hippocampal pyramidal neurons. Biophysical Society 60th Annual Meeting, Los Angeles 2016.
Link to PubMed Publications