Voltage-Activated Calcium Channels as Functional Markers of Mature Neurons in Human Olfactory Neuroepithelial Cells: Implications for the Study of Neurodevelopment in Neuropsychiatric Disorders.
In adulthood, differentiation of precursor cells into neurons continues in several brain structures as well as in the olfactory neuroepithelium. Isolated precursors allow the study of the neurodevelopmental process in vitro. The aim of this work was to determine whether the expression of functional Voltage-Activated Ca(2+) Channels (VACC) is dependent on the neurodevelopmental stage in neuronal cells obtained from the human olfactory epithelium of a single healthy donor. The presence of channel-forming proteins in Olfactory Sensory Neurons (OSN) was demonstrated by immunofluorescent labeling, and VACC functioning was assessed by microfluorometry and the patch-clamp technique. VACC were immunodetected only in OSN. Mature neurons responded to forskolin with a five-fold increase in Ca(2+). By contrast, in precursor cells, a subtle response was observed. The involvement of VACC in the precursors' response was discarded for the absence of transmembrane inward Ca(2+) movement evoked by step depolarizations. Data suggest differential expression of VACC in neuronal cells depending on their developmental stage and also that the expression of these channels is acquired by OSN during maturation, to enable specialized functions such as ion movement triggered by membrane depolarization. The results support that VACC in OSN could be considered as a functional marker to study neurodevelopment.
Laboratorio de Neurofarmacolog&#237;a, Instituto Nacional de Psiquiatr&#237;a Ram&#243;n de la Fuente Mu&#241;iz, Calzada M&#233;xico-Xochimilco No. 101, Col. San Lorenzo-Huipulco, Mexico City 14370, Mexico. hecsolch@imp.edu.mx.
Héctor
H
Solís-Chagoyán
Departamento de Farmacolog&#237;a, Facultad de Medicina, Universidad Nacional Aut&#243;noma de M&#233;xico, Mexico City 04510, Mexico. edgarfloressoto@yahoo.com.mx.
Edgar
E
Flores-Soto
Departamento de Farmacolog&#237;a, Facultad de Medicina, Universidad Nacional Aut&#243;noma de M&#233;xico, Mexico City 04510, Mexico. reyes.garcia.jorge@gmail.com.
Jorge
J
Reyes-García
Laboratorio de Neurofarmacolog&#237;a, Instituto Nacional de Psiquiatr&#237;a Ram&#243;n de la Fuente Mu&#241;iz, Calzada M&#233;xico-Xochimilco No. 101, Col. San Lorenzo-Huipulco, Mexico City 14370, Mexico. mvaldes@imp.edu.mx.
Marcela
M
Valdés-Tovar
Departamento de Neurobiolog&#237;a, Instituto Nacional de Psiquiatr&#237;a Ram&#243;n de la Fuente Mu&#241;iz, Calzada M&#233;xico-Xochimilco No. 101, Col. San Lorenzo-Huipulco, Mexico City 14370, Mexico. ecalixto@imp.edu.mx.
Eduardo
E
Calixto
Departamento de Farmacolog&#237;a, Facultad de Medicina, Universidad Nacional Aut&#243;noma de M&#233;xico, Mexico City 04510, Mexico. lmmr@unam.mx.
Luis M
LM
Montaño
Laboratorio de Neurofarmacolog&#237;a, Instituto Nacional de Psiquiatr&#237;a Ram&#243;n de la Fuente Mu&#241;iz, Calzada M&#233;xico-Xochimilco No. 101, Col. San Lorenzo-Huipulco, Mexico City 14370, Mexico. bekin@imp.edu.mx.
Gloria
G
Benítez-King
D015415:Biomarkers / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism*
D015415:Biomarkers; D015220:Calcium Channels
calcium flux; differentiation process; human precursors; neuronal excitability; neuropsychiatric disorders; voltage-gated Ca2+ channels