Warm temperatures activate TRPV4 in mouse 308 keratinocytes.
Mammalian survival requires constant monitoring of environmental and body temperature. Recently, several members of the transient receptor potential vanilloid (TRPV) subfamily of ion channels have been identified that can be gated by increases in temperature into the warm (TRPV3 and TRPV4) or painfully hot (TRPV1 and TRPV2) range. In rodents, TRPV3 and TRPV4 proteins have not been detected in sensory neurons but are highly expressed in skin epidermal keratinocytes. Here, we show that in response to warm temperatures (>32 degrees C), the mouse 308 keratinocyte cell line exhibits nonselective transmembrane cationic currents and Ca2+ influx. Both TRPV3 and TRPV4 are expressed in 308 cells. However, the warmth-evoked responses we observe most closely resemble those mediated by recombinant TRPV4 on the basis of their electrophysiological properties and sensitivity to osmolarity and the phorbol ester, 4alpha-phorbol-12,13-didecanoate. Together, these data support the notion that keratinocytes are capable of detecting modest temperature elevations, strongly suggest that TRPV4 participates in these responses, and define a system for the cell biological analysis of warmth transduction.
Chung
Man-Kyo
MK
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
Lee
Hyosang
H
Caterina
Michael J
MJ
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D027682:Cation Transport Proteins; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D006358:Hot Temperature; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism* / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D050916:TRPV Cation Channels
D027682:Cation Transport Proteins; D017931:DNA Primers; D007473:Ion Channels; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; C486576:Trpv4 protein, mouse; D002118:Calcium