Activity and Ca2+ regulate the mobility of TRPV1 channels in the plasma membrane of sensory neurons

TRPV1 channels are gated by a variety of thermal, chemical, and mechanical stimuli. We used optical recording of Ca(2+) influx through TRPV1 to measure activity and mobility of single TRPV1 molecules in isolated dorsal root ganglion neurons and cell lines. The opening of single TRPV1 channels produced sparklets, representing localized regions of elevated Ca(2+). Unlike sparklets reported for L-type Ca(2+) channels, TRPV4 channels, and AchR channels, TRPV1 channels diffused laterally in the plasma membrane as they gated. Mobility was highly variable from channel-to-channel and, to a smaller extent, from cell to cell. Most surprisingly, we found that mobility decreased upon channel activation by capsaicin, but only in the presence of extracellular Ca(2+). We propose that decreased mobility of open TRPV1 could act as a diffusion trap to concentrate channels in cell regions with high activity.