Toxin Ct1a, from venom of Centruroides tecomanus, modifies the spontaneous firing frequency of neurons in the suprachiasmatic nucleus.

Autor: Alamilla J; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col, Mexico; Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico., Jiménez-Vargas JM; Consejo Nacional de Ciencia y Tecnología (CONACYT), Mexico; Facultad de Ciencias Químicas, Universidad de Colima, Coquimatlán, Colima, Mexico., Galván-Hernández AR; Facultad de Ciencias Químicas, Universidad de Colima, Coquimatlán, Colima, Mexico., Reyes-Méndez ME; Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima, Col, Mexico., Bermúdez-Gúzman MJ; Facultad de Ciencias Químicas, Universidad de Colima, Coquimatlán, Colima, Mexico., Restano-Cassulini R; Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico., Olamendi-Portugal T; Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico., Zamudio FZ; Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico., Possani LD; Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico., Valdez-Velázquez LL; Facultad de Ciencias Químicas, Universidad de Colima, Coquimatlán, Colima, Mexico. Electronic address: lauravaldez@ucol.mx.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2021 Jul 15; Vol. 197, pp. 114-125. Date of Electronic Publication: 2021 Apr 23.
DOI: 10.1016/j.toxicon.2021.04.015
Abstrakt: The peptide, denominated Ct1a, is a β-toxin of 66 amino acids, isolated from venom of the scorpion, Centruroides tecomanus, collected in Colima, Mexico. This toxin was purified using size exclusion, cationic exchange, and reverse phase chromatography. It is the most abundant toxin, representing 1.7% of the soluble venom. Its molecular mass of 7588.9 Da was determined by mass spectrometry. The amino acid sequence was determined by Edman degradation and confirmed by transcriptomic analysis. Since neurons of the suprachiasmatic nucleus (SCN) maintain a spontaneous firing rate (SFR), we evaluated the physiological effects of toxin Ct1a on these neurons. The SFR exhibited a bimodal concentration-dependent response: 100 nM of Ct1a increased the SFR by 223%, whereas 500 nM and 1000 nM reduced it to 42% and 7%, respectively. Control experiments, consisting of recordings of the SFR during a time similar to that used in Ct1a testing, showed stability throughout the trials. Experiments carried out with denatured Ct1a toxin (500 nM) caused no variation in SFR recordings. Action potentials of SCN neurons, before and after Ct1a (100 nM) showed changes in the time constants of depolarization and repolarization phases, amplitude, and half-time. Finally, recordings of hNav1.6 sodium currents indicated that Ct1a shifts the channel activation to a more negative potential and reduces the amplitude of the peak current. These results all demonstrate that toxin Ct1a affects the SFR of SCN neurons by acting upon sodium channels of sub-type 1.6, implicating them in regulation of the SFR of SCN neurons.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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