Abstract
TRPP3 channels or PKD2L1 channels, with high homology to another member of TRPP family, PKD2 (named after polycystic kidney disease), play potential roles in sour taste. TRPP3 channels are highly regulated by calcium, complicated with both calcium dependent activation and inactivation (Chen XZ, et al. 1999). However, the essential mechanisms of these calcium regulations are lacking (Li Q, et al., 2002). In this study, we took advantage of the unique off-response (Ioff) evoked by acid stimuli onto TRPP3 channels expressed in HEK 293 cells, to dissect the calcium dependent inactivation (CDI) from the complex calcium responses evidenced in oocyte preparations. By changing extracellular calcium concentrations from 0 to 110 mM, and intracellular buffers from EGTA to BAPTA, we proved that the decaying phase of Ioff is completely calcium dependent. We tested and then rejected the hypothesis that calmodulin mediates the CDI of TRPP3 channels, by overexpressing the mutant form of calmodulin. Further mutagenesis analyses revealed that CDI would be abolished when the interactions between intracellular calcium ions and the EF-hand of carboxyl termini of TRPP3 channels were perturbed. Our work not only provides mechanistic insights into CDI of Ioff, but also paves the way to the elucidation of calcium-dependent activation, thus the ultimate resolution of calcium-dependent regulations of TRPP3 channels.
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