Mechanisms of activation and modulation of the TRPV1 receptor: relationship between structure and function

Vanilloid Receptor Subtype 1 - TRPV1 - is an important member of the TRP ion channel family. The physiological role of this ion channel is to integrate the nociceptive signals from the peripheral nervous system. TRPV1 participates in the detection of noxious stimuli on the primary afferent sensory neurons: of the chemical stimuli, such as capsaicin, resiniferatoxin, inflammatory mediators, endogenous vanilloids, and of the low pH (43řC). Apart from the high expression on the dorsal root ganglion neurons and trigeminal ganglions, the functional expression of this receptor has been also found in the central nervous system, where its role remains elusive, however. Structural-functional studies which have been carried out since the receptor was first cloned, that is 13 years ago, have revealed several specific characteristics. Nonetheless, a number of questions remain to be answered, particularly those concerning cellular mechanisms and regulation of TRPV1's activation, modulation, and its complex function in the nervous system. The aim of this diploma thesis was to characterize, using electrophysiological and fluorescence techniques, the activation and desensitization kinetics of recombinant TRPV1 receptor in relation to the dynamic changes of intracellular calcium...