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Abstract:

Human postmortem studies reported increased expression of neuronal calcium sensor protein 1 (NCS-1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Lithium (Li+) has been shown to effectively treat the mood disturbances in bipolar disorder patients and was proposed to act by inhibiting the interaction between NCS-1 and inositol 1,4,5-triphosphate receptor protein (InsP3R). NCS-1 is known to enhance the activity of InsP3R, and of Ca2+-mediated gamma oscillatory activity in the pedunculopontine nucleus (PPN), part of the RAS. This study aimed to determine the nature of some of the intracellular mechanisms of Li+ on rat PPN cells and to identify the interaction between Li+ and NCS-1. Since Li+ has been shown to act by inhibiting the enhancing effects of NCS-1, we tested the hypothesis that Li+ would reduced the effects of overexpression of NCS-1 and prevent the downregulation of gamma band activity. Li+ decreased gamma oscillation frequency and amplitude by downregulating Ca2+ channel activity, whereas NCS-1 reduced the effect of Li+ on Ca2+ currents. These effects were mediated by a G-protein overinhibition of Ca2+ currents. These results suggest that Li+ affected intracellular pathways involving the activation of voltage-gated Ca2+ channels mediated by an intracellular mechanism involving voltage-dependent activation of G proteins, thereby normalizing gamma band oscillations mediated by P/Q-type calcium channels modulated by NCS-1. © 2016 Published by the American Physiological Society and The Physiological Society.

Registro:

Documento: Artículo
Título:Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons
Autor:D'Onofrio, S.; Urbano, F.J.; Messias, E.; Garcia-Rill, E.
Filiación:Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
IFIBYNE-CONICET-UBA, University of Buenos Aires, Buenos Aires, Argentina
Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, United States
Palabras clave:Bipolar disorder; Gamma band activity; Sleep/wake; calcium channel N type; frequenin calcium sensor proteins; lithium derivative; neuroleptic agent; neuronal calcium sensor; neuropeptide; recombinant protein; voltage-dependent calcium channel (P-Q type); animal; calcium signaling; channel gating; dose response; drug effects; female; gamma rhythm; in vitro study; kinetics; male; membrane potential; metabolism; nerve cell; newborn; pedunculopontine tegmental nucleus; Sprague Dawley rat; Animals; Animals, Newborn; Antipsychotic Agents; Calcium Channels, N-Type; Calcium Signaling; Dose-Response Relationship, Drug; Female; Gamma Rhythm; In Vitro Techniques; Ion Channel Gating; Kinetics; Lithium Compounds; Male; Membrane Potentials; Neuronal Calcium-Sensor Proteins; Neurons; Neuropeptides; Pedunculopontine Tegmental Nucleus; Rats, Sprague-Dawley; Recombinant Proteins
Año:2016
Volumen:4
Número:6
Página de inicio:1
Página de fin:12
DOI: http://dx.doi.org/10.14814/phy2.12740
Título revista:Physiological Reports
Título revista abreviado:Physiol. Rep.
ISSN:2051817X
CAS:Antipsychotic Agents; Calcium Channels, N-Type; frequenin calcium sensor proteins; Lithium Compounds; Neuronal Calcium-Sensor Proteins; Neuropeptides; Recombinant Proteins; voltage-dependent calcium channel (P-Q type)
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_2051817X_v4_n6_p1_DOnofrio

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Citas:

---------- APA ----------
D'Onofrio, S., Urbano, F.J., Messias, E. & Garcia-Rill, E. (2016) . Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons. Physiological Reports, 4(6), 1-12.
http://dx.doi.org/10.14814/phy2.12740
---------- CHICAGO ----------
D'Onofrio, S., Urbano, F.J., Messias, E., Garcia-Rill, E. "Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons" . Physiological Reports 4, no. 6 (2016) : 1-12.
http://dx.doi.org/10.14814/phy2.12740
---------- MLA ----------
D'Onofrio, S., Urbano, F.J., Messias, E., Garcia-Rill, E. "Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons" . Physiological Reports, vol. 4, no. 6, 2016, pp. 1-12.
http://dx.doi.org/10.14814/phy2.12740
---------- VANCOUVER ----------
D'Onofrio, S., Urbano, F.J., Messias, E., Garcia-Rill, E. Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons. Physiol. Rep. 2016;4(6):1-12.
http://dx.doi.org/10.14814/phy2.12740