Mechanotransduction in situ

Activity Code: FP7-PEOPLE-2009-IEF
Coordinator:Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch

Abstract:

Mechano-transduction is the conversion of mechanical force into a cellular response. Many physiological processes involve mechano-transduction such as touch, pain, hearing and balance. Touch receptors are sensory neurons with their cell somas in the dorsal root and trigeminal ganglia and their axons innervating somatic tissues, like the skin. Sensory information is sent to the central nervous system but transduction is far removed from the soma. Due to this anatomy, direct study of mechano-transduction in situ has not yet been possible. Here we will clarify the physiological basis of the mechano-transduction by using a novel experimental approach to overcome these technical limitations. We will set-up an electrophysiological preparation in which the site of transduction is close enough to the ganglion cell body to measure intra-cellularly single-cell responses to mechanical stimulation. We will dissect out mouse DRG neurons and transplant them into the skin of a host mouse.

After innervation of the host skin, skin innervated by transplanted sensory neurons will be prepared and mechano-transduction currents in the transplanted neurons will be recorded using the patch-clamp technique. We will be able, therefore, to stimulate mechanoreceptors with their endings embedded in the skin as occurs in vivo, while recorded from the cell soma. For the first time, we will measure the electrophysiological properties of mechano-sensitive ion channels upon physiological stimulation as well as the firing properties of the same mechanoreceptors in current clamp mode. Moreover, using genetically-labeled DRG neurons, we will be able to examine mechano-transduction in different classes of mechanoreceptors or nociceptors. Moreover, given that pain is often evoked by light touch under neuropathic conditions our results will also clarify the physiological mechanisms of transduction of painful sensation, raising the possibility of testing novel methods and drugs to treat sensory disorders.

Project Details:

Start Date: 01.08.2010
End Date: 31.07.2012
EU Contribution: 161,661 Euro
Total Costs: 161,661 Euro
Funding Scheme: Intra-European Fellowships (IEF)
Scientific Contact: Prof. Dr Gary Richard Lewin, glewin@mdc-berlin.de