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Access to the sensory nerve terminals of unmyelinated axons has been limited by their size (<0.5µm) and indeterminate location. However, a methodological development led by Prof. James Brock has recently enabled extracellular recordings from individual unmyelinated nerve terminals in the cornea using a loose patch recording technique. All terminal axons within the cornea are unmyelinated and sensory endings with mechanical, cold, chemo and polymodal sensitivity have been described. The limited number of studies to date have shown that the terminals of polymodal and cold receptors express both tetrodotoxin sensitive (TTX-s) and TTX resistant (TTX-r) voltage gated sodium channel (NaV) subtypes and that TTX-r NaVs are alone sufficient for the initiation of action potentials (AP). The site of AP initiation has also been examined using this technique and was shown to be spatially labile, shifting in cold receptors towards the nerve terminal tip during warming and deeper into the tissue during cooling as membrane potential changes the number of available NaVs.
Two ongoing projects combine this unique electrophysiological technique with mathematical modeling. The first looks at the role of persistent sodium current in generating spontaneous activity in nociceptors. The second project incorporates transgenic mouse lines to decipher the process of stimulus encoding in sensory nerve terminals.
PD Dr. Richard Carr