RESUMEN
Sarafotoxins (SRTXs) constitute a family of vasoactive peptides that were initially isolated from the venom of Atractaspis engaddensis, and that are structurally and functionally related to endothelins (ETs). Analysis of the venom of Atractaspis microlepidota microlepidota revealed several new SRTX molecules manifesting some new structural and functional characteristics. These novel SRTXs are longer by three amino acids than the previously described SRTXs, and are designated here "long-SRTXs". Six isoforms, derived from new poly-cistronic precursors, have been identified so far in the venom of this snake. One of these isoforms, designated SRTX-m, was chemically synthesized and its biological properties were studied. Our results show that SRTX-m induces toxicity in mice, mostly due to vasoconstriction, and also that it has a lower toxicity and potency than the more potent SRTX described up to now: sarafotoxin-b (SRTX-b) from A. engaddensis.
Asunto(s)
Endotelinas/química , Péptidos/química , Venenos de Víboras/química , Secuencia de Aminoácidos , Animales , Relación Dosis-Respuesta a Droga , Endotelinas/toxicidad , Frecuencia Cardíaca/efectos de los fármacos , Ratones , Datos de Secuencia Molecular , Contracción Muscular/efectos de los fármacos , Péptidos/genética , Péptidos/toxicidad , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/toxicidad , Conejos , Serpientes , Vasoconstrictores/química , Vasoconstrictores/toxicidad , Venenos de Víboras/genética , Venenos de Víboras/toxicidadRESUMEN
The mole rat (Spalax ehrenbergi) is a subterranean rodent whose adaptations to its fossorial life include an extremely reduced peripheral visual system and an auditory system suited for the perception of vibratory stimuli. We have previously shown that in this blind rodent the dorsal lateral geniculate nucleus, the primary visual thalamic nucleus of sighted mammals, is activated by auditory stimuli. In this report we focus on the manifestation of this cross-modal compensation at the cortical level. Cyto- and myeloarchitectural analyses of the occipital area showed that despite the almost total blindness of the mole rat this area has retained the organization of a typical mammalian primary visual cortex. Application of the metabolic marker 2-deoxyglucose and electrophysiological recording of evoked field potentials and single-unit activity disclosed that a considerable part of this area is activated by auditory stimuli. Previous neuronal tracing studies had revealed the origin of the bulk of this auditory input to be the dorsal lateral geniculate nucleus which itself receives auditory input from the inferior colliculus.
Asunto(s)
Vías Auditivas/fisiología , Percepción Auditiva/fisiología , Ceguera/fisiopatología , Ratas Topo/fisiología , Plasticidad Neuronal/fisiología , Corteza Visual/fisiología , Vías Visuales/fisiología , Estimulación Acústica , Potenciales de Acción/fisiología , Animales , Corteza Auditiva/citología , Corteza Auditiva/fisiología , Vías Auditivas/citología , Mapeo Encefálico , Adaptación a la Oscuridad/fisiología , Desoxiglucosa , Potenciales Evocados Auditivos/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Mecanorreceptores/fisiología , Ratas Topo/anatomía & histología , Neuronas/citología , Neuronas/fisiología , Estimulación Física , Corteza Somatosensorial/citología , Corteza Somatosensorial/fisiología , Vibrisas/fisiología , Corteza Visual/citología , Vías Visuales/citologíaRESUMEN
Potential auditory compensation in neonatally bilaterally enucleated Syrian hamsters was explored anatomically, electrophysiologically and behaviourally. Gross morphology of the visual cortex appeared normal and no obvious cytoarchitectural malformation was discerned. However, enucleation induced a significant increase in the spontaneous firing rate of visual cortex cells. Further, auditory stimuli elicited field potentials and single unit responses in the visual cortex of enucleated, but not normal, animals. About 63% of the cells isolated in the visual cortex of 16 enucleated hamsters responded to at least one type of auditory stimulus. Most of the responses were less vigorous and less time-locked than those of auditory cortex cells, and thresholds were typically higher. Projection tracing with WGA-HRP disclosed reciprocal connections between the visual cortex and the dorsal lateral geniculate nucleus in both intact and enucleated animals. However, in the enucleated animals retrogradely labelled cells were also found in the inferior colliculus, the major midbrain auditory nucleus. Behaviourally determined auditory sensitivity across the hearing range did not differ between enucleated and intact hamsters. Minimum audible angle, as determined by a conditioned suppression task, ranged from around 17 to 22 degrees, with no significant difference between normal and enucleated animals. The two groups also did not differ with regard to the direction of their unconditioned head orientating response to intermittent noise. However, the enucleated animals showed a more vigorous response and were slower to habituate to the noise. These results show that bilateral enucleation of newborn hamsters results in auditory activation of visual targets, in addition to the typical activation of the intact auditory pathway. Behaviourally it appears that enucleated hamsters, compared with their normal littermates, are slower to habituate in their response to an unexpected source of sound.
Asunto(s)
Vías Auditivas/fisiología , Conducta Animal/fisiología , Enucleación del Ojo/efectos adversos , Cuerpos Geniculados/fisiopatología , Colículos Inferiores/fisiopatología , Plasticidad Neuronal/fisiología , Vías Visuales/lesiones , Potenciales de Acción/fisiología , Animales , Animales Recién Nacidos , Atrofia/etiología , Atrofia/patología , Atrofia/fisiopatología , Corteza Auditiva/citología , Corteza Auditiva/fisiología , Vías Auditivas/citología , Percepción Auditiva/fisiología , Cricetinae , Femenino , Cuerpos Geniculados/patología , Colículos Inferiores/patología , Masculino , Neuronas/fisiología , Nervio Óptico/patología , Nervio Óptico/fisiopatología , Tiempo de Reacción/fisiología , Recuperación de la Función/fisiología , Corteza Visual/citología , Corteza Visual/fisiología , Vías Visuales/patología , Vías Visuales/fisiopatología , Percepción Visual/fisiología , Degeneración Walleriana/etiología , Degeneración Walleriana/patología , Degeneración Walleriana/fisiopatologíaRESUMEN
In addition to visually driven cells we found within the lateral suprasylvian visual cortex of cats a considerable number of auditory and/or bimodal cells. Most of the visually driven cells were direction and orientation selective with responses that were neither highly stimulus time locked nor very stable. Most of the auditory responses were also not very stable, had relatively high thresholds, and were readily habituated. Previous studies have suggested that populations of cells within the lateral suprasylvian area are specialized for the analysis of optic flow fields (Rauscheker et al., 1987; Sherk et al., 1995). Given that a remarkable proportion of cells within this area can be also driven by auditory stimuli, we hypothesize that the 'optic flow' model may be extended to the bimodal domain rather than restricted to visual clues only. This, however, remains to be corroborated experimentally.