ΔN-TRPV1: A Molecular Co-detector of Body Temperature and Osmotic Stress
Cristian Zaelzer,
Pierce Hua,
Masha Prager-Khoutorsky,
Sorana Ciura,
Daniel L. Voisin,
Wolfgang Liedtke,
Charles W. Bourque
Affiliations
Cristian Zaelzer
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada
Pierce Hua
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada
Masha Prager-Khoutorsky
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada
Sorana Ciura
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada
Daniel L. Voisin
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada
Wolfgang Liedtke
Department of Neurology and Center for Translational Neuroscience, 201G Bryan Research Building, Box 2900, Duke University Medical Center, Durham, NC 27710, USA
Charles W. Bourque
Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, 1650 Cedar Avenue, Montreal, QC H3G1A4, Canada
Thirst and antidiuretic hormone secretion occur during hyperthermia or hypertonicity to preserve body hydration. These vital responses are triggered when hypothalamic osmoregulatory neurons become depolarized by ion channels encoded by an unknown product of the transient receptor potential vanilloid-1 gene (Trpv1). Here, we show that rodent osmoregulatory neurons express a transcript of Trpv1 that mediates the selective translation of a TRPV1 variant that lacks a significant portion of the channel’s amino terminus (ΔN-TRPV1). The mRNA transcript encoding this variant (Trpv1dn) is widely expressed in the brains of osmoregulating vertebrates, including the human hypothalamus. Transfection of Trpv1dn into heterologous cells induced the expression of ion channels that could be activated by either hypertonicity or by heating in the physiological range. Moreover, expression of Trpv1dn rescued the osmosensory and thermosensory responses of single hypothalamic neurons obtained from Trpv1 knockout mice. ΔN-TRPV1 is therefore a co-detector of core body temperature and fluid tonicity.
