Epidermal keratinocyte polarity and motility require Ca2+ influx through TRPV1

Ca2+ has long been known to play an important role in cellular polarity and guidance. We studied the role of Ca2+ signaling during random and directed cell migration to better understand whether Ca2+ directs cell motility from the leading edge and which ion channels are involved in this function by using primary zebrafish keratinocytes. Rapid line-scan and time-lapse imaging of intracellular Ca2+ (Ca-i(2+)) during migration and automated image alignment enabled us to characterize and map the spatiotemporal changes in Ca-i(2+). We show that asymmetric distributions of lamellipodial Ca2+ sparks are encoded in frequency, not amplitude, and that they correlate with cellular rotation during migration. Directed migration during galvanotaxis increases the frequency of Ca2+ sparks over the entire lamellipod; however, these events do not give rise to asymmetric Ca-i(2+) signals that correlate with turning. We demonstrate that Ca2+-permeable channels within these cells are mechanically activated and include several transient receptor potential family members, including TRPV1. Last, we demonstrate that cell motility and Ca-i(2+) activity are affected by pharmacological agents that target TRPV1, indicating a novel role for this channel during cell migration.