| Popis: |
TRPA1 is the only mammalian member of the ankyrin type subfamily of transient receptor potential (TRP) ion channels. This channel is widely expressed in many cell types and tissues, including sensory neurones, heart, brain, and lung, where it detects stimuli of different sensory modalities, including a broad spectrum of potentially harmful irritants and pungent compounds, such as isothiocyanates, thiosulfinates, acrolein, cinnamaldehyde derivatives, eugenol, nicotine, as well as multiple products of oxidative stress. In addition to these chemicals, TRPA1 channel can be also activated and, concurrently, inhibited by intracellular calcium, however, the exact mechanisms of this regulation are still unclear. TRPA1 is a nonselective cation channel, permeable for calcium ions, however, relative scattered data on TRPA1 channel selectivity provide divergent estimates ranging from 0,84 to 7,9; in addition, these values strongly depend on the activation mode of the channel. It appears that the extent to which calcium ions dynamically modulate TRPA1 depends on the total amount of cations permeating the ion channel pore. This diploma thesis contributes to the understanding of this topic by (i) investigating the effects of extracellular calcium ions on chemically and voltage- induced activity of human TRPA1... |
