Characterization and modulation of voltage-gated potassium channels in human lymphocytes in schizophrenia.

Autor: Iglesias-Martínez-Almeida M; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain; University of Vigo, Vigo, Spain., Campos-Ríos A; Laboratory of neuroscience, University of Vigo, Department of Functional Biology and Health Sciences, Vigo, Spain; Laboratory of Neuroscience, Galicia Sur Health Research Institute (IISGS), SERGAS-UVIGO, Vigo, Spain., Freiría-Martínez L; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain; University of Vigo, Vigo, Spain., Rivera-Baltanás T; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain; University of Vigo, Vigo, Spain; CIBERSAM, Madrid, Spain., Rodrígues-Amorím D; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States., Diz-Chaves Y; Laboratory of Endocrinology, CINBIO, University of Vigo, Vigo, Spain., Comis-Tuche M; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., Fernández-Palleiro P; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., Rodríguez-Jamardo C; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain; University of Vigo, Vigo, Spain., Ramos-García S; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., Rodríguez-Tébar A; Microscopy Service, Galicia Sur Health Research Institute (IISGS), Vigo, Spain., Del Carmen Vallejo-Curto M; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., Campos-Pérez JA; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., López-García M; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., de Las Heras E; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., García-Caballero A; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain., Olivares JM; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain; CIBERSAM, Madrid, Spain., Lamas JA; Laboratory of neuroscience, University of Vigo, Department of Functional Biology and Health Sciences, Vigo, Spain; Laboratory of Neuroscience, Galicia Sur Health Research Institute (IISGS), SERGAS-UVIGO, Vigo, Spain., Spuch C; Translational Neuroscience Group, Galicia Sur Health Research Institute (IIS Galicia Sur), SERGAS-UVIGO, Vigo, Spain; CIBERSAM, Madrid, Spain. Electronic address: carlos.spuch@iisgaliciasur.es.
Jazyk: angličtina
Zdroj: Schizophrenia research [Schizophr Res] 2024 Aug; Vol. 270, pp. 260-272. Date of Electronic Publication: 2024 Jun 29.
DOI: 10.1016/j.schres.2024.06.034
Abstrakt: Background: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia.
Methods: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit β1 (KCNAB1) and β2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells.
Results: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls.
Conclusions: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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