RESUMO
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.
Assuntos
Hipotálamo/metabolismo , Neurônios/metabolismo , Osmorregulação/fisiologia , Pressão Osmótica/fisiologia , Canais de Cátion TRPV/genética , Potenciais de Ação/fisiologia , Sequência de Aminoácidos , Animais , Temperatura Corporal , Tamanho Celular , Feto , Regulação da Expressão Gênica , Células HEK293 , Temperatura Alta , Humanos , Hipotálamo/citologia , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Neurônios/citologia , Técnicas de Patch-Clamp , Cultura Primária de Células , Biossíntese de Proteínas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratos , Ratos Long-Evans , Alinhamento de Sequência , Transdução de Sinais , Canais de Cátion TRPV/metabolismoRESUMO
Recent evidence has been accumulated that not only spinal trigeminal nucleus caudalis (Sp5C) neurons but also spinal trigeminal nucleus oralis (Sp5O) neurons respond to noxious stimuli. It is unknown, however, whether Sp5O neurons project to supratrigeminal structures implicated in the sensory processing of orofacial nociceptive information. This study used retrograde tracing with Fluorogold in rats to investigate and compare the projections from the Sp5O and Sp5C to two major thalamic nuclei that relay ascending somatosensory information to the primary somatic sensory cortex: the ventroposteromedial thalamic nucleus (VPM) and the posterior thalamic nuclear group (Po). Results not only confirmed the existence of contralateral projections from the Sp5C to the VPM and Po, with retrogradely labelled neurons displaying a specific distribution in laminae I, III and V, they also showed consistent and similar numbers of retrogradely labelled cell bodies in the contralateral Sp5O. In addition, a topographic distribution of VPM projections from Sp5C and Sp5O was found: neurons in the dorsomedial parts of Sp5O and Sp5C projected to the medial VPM, neurons in the ventrolateral Sp5O and Sp5C projected to the lateral VPM, and neurons in intermediate parts of Sp5O and Sp5C projected to the intermediate VPM. All together, these data suggest that not only the Sp5C, but also the Sp5O relay somatosensory orofacial information from the brainstem to the thalamus. Furthermore, trigemino-VPM pathways conserve the somatotopic distribution of primary afferents found in each subnucleus. These results thus improve our understanding of trigeminal somatosensory processing and help to direct future electrophysiological investigations.
Assuntos
Potenciais Somatossensoriais Evocados/fisiologia , Tálamo/fisiologia , Núcleo Inferior Caudal do Nervo Trigêmeo/fisiologia , Animais , Masculino , Vias Neurais/fisiologia , Ratos , Ratos Sprague-Dawley , Núcleo Espinal do Trigêmeo/fisiologiaRESUMO
Vasopressin (antidiuretic hormone) release has been thought to be controlled by interacting osmoreceptors and Na(+)-detectors for > 20 years. Only recently, however, have molecular and cellular advances revealed how changes in the external concentration of Na+ and osmolality are detected during acute and chronic osmotic perturbations. In rat vasopressin-containing neurons, local osmosensitivity is conferred by intrinsic stretch-inactivated cation channels and by taurine release from surrounding glia. Na+ detection is accomplished by acute regulation of the permeability of stretch-inactivated channels and by changes in Na+ channel gene expression. These features provide a first glimpse of the integrative processes at work in a central osmoregulatory reflex.