ΔN-TRPV1: A Molecular Co-detector of Body Temperature and Osmotic Stress

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. [Display omitted] •Osmoregulatory neurons express ΔN-TRPV1, a capsaicin-insensitive cation channel•ΔN-TRPV1 channels are activated by physiological heat and cell shrinking•Expression of Trpv1dn rescues osmoreception and thermosensing in Trpv1−/− mice Osmoregulation requires that thirst and vasopressin release be evoked in response to a rise in body temperature or fluid tonicity. In this study, Zaelzer et al. reveal that single hypothalamic osmoregulatory neurons can detect physiologically relevant increases in osmolality and temperature through the expression of an alternate transcript of Trpv1.