The goal of this Phase 1 SBIR is to design and test a prototype of the Channel Laser Stimulator capable of stimulating single cells or part of the cell. This tool is needed to study dose dependency of heat/capsaicin-sensitive cells/neurons and """"""""calcium"""""""" channels. Understanding how these """"""""calcium"""""""" channels work and principles of their kinetics is important in neuroscience in general and especially in therapeutics and drug development. Further, the development of this instrument will enable the manipulation of cell activity in culture or in tissues with light, a method that could lead to important new applications for regulating cellular or physiological processes in vivo. This device may also lead to novel methods of drug screening and development as it could provide a rapid, well calibrated, and reproducible method of delivering a thermal pulse to cells or purified ion channel protein in single or multi-well format. We will design and test a Channel Laser Stimulator that (A) will deliver a consistent light intensity directly to the target-membrane and channels of the cell; (B) will enable the operator to precisely control the heat stimulus and thus activate some (predictable) amount of channel activity; and (C) will enable the operator to calibrate heat stimulus by power and pulse duration of the laser pulses. We will design this prototype of the Channel Laser Stimulator with parameters optimized for single cell level research, based on (1) the design of an infrared laser diode pain stimulator, developed by LASMED, and (2) the results of preliminary testing. We will consult with a leading scientist in the field of molecular investigations of thermo sensitive ion channels in the mammalian nervous system. All necessary tests to verify performance of the Channel Laser Stimulator will be carried out in the laboratory of this scientist by his personnel.
Zhang, Jie; Cavanaugh, Daniel J; Nemenov, Michael I et al. (2013) The modality-specific contribution of peptidergic and non-peptidergic nociceptors is manifest at the level of dorsal horn nociresponsive neurons. J Physiol 591:1097-110 |
Mitchell, Kendall; Bates, Brian D; Keller, Jason M et al. (2010) Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates. Mol Pain 6:94 |
Cuellar, Jason M; Manering, Neil A; Klukinov, Mikhail et al. (2010) Thermal nociceptive properties of trigeminal afferent neurons in rats. Mol Pain 6:39 |