Role of Calcium Channels in Bipolar Disorder

Abstract

Bipolar disorder is characterized by a host of sleep-wake abnormalities that suggests that the reticular activating system (RAS) is involved in these symptoms. One of the signs of the disease is a decrease in high frequency gamma band activity, which accounts for a number of additional deficits. Bipolar disorder has also been found to overexpress neuronal calcium sensor protein 1 (NCS-1). Recent studies showed that elements in the RAS generate gamma band activity that is mediated by high threshold calcium (Ca2+) channels. This mini-review provides a description of recent findings on the role of Ca2+ and Ca2+ channels in bipolar disorder, emphasizing the involvement of arousal-related systems in the manifestation of many of the disease symptoms. This will hopefully bring attention to a much-needed area of research and provide novel avenues for therapeutic development.

NCS-1 is a regulator of calcium signaling in health and disease

“…Post mortem studies found increased levels of NCS-1 in the prefrontal cortex of bipolar and schizophrenic patients [61]. Furthermore, NCS-1 has been implicated in sleep-wake disturbance symptoms in bipolar disease [62] and this interaction could contribute the effectiveness of lithium in treating bipolar disorder patients [63]. Mutations in Interleukin-1 Receptor Accessory Protein-Like 1 (IL1RAPL1), one of NCS-1’s target proteins, are associated with a wide range of neurological impairments [64].…”

Principales componentes del Trastorno Bipolar

“…5 La patología se puede entender como una serie de eventos concatenados, la cual provoca un desequilibrio en el organismo manifestándose con la irregularidad del ritmo sueño-vigilia, el cronotipo vespertino, irregularidades de las señales del tiempo social, alteraciones en el eje hipotálamo-pituitario-adrenal, y alteraciones en la emoción, sensación y percepción. 6,7,8 Se han identificado al menos 30 loci asociados al trastorno bipolar que codifican canales iónicos, transportadores de neurotransmisores y componentes sinápticos; los genes más estudiados y con más relación son: 9 CACNA1C: Codificador de la subunidad a1 de los canales de calcio tipo L, relacionado a la entrada de calcio e hiperpolarización celular. ANK3: Codifica anquirina G, que acopla los canales de sodio axonales activados por voltaje al citoesqueleto y también tiene funciones en las dendritas y la glía.…”

Pharmacogenetics of Carbamazepine and Valproate: Focus on Polymorphisms of Drug Metabolizing Enzymes and Transporters

“…CBZ and VPA could exert their effects also by directly modulating voltage-dependent calcium channels. Ca 2+ channels are particularly represented on pre-synaptic neurons, are involved in neuronal depolarization and play an important role in epilepsy [ 23 , 24 ]. For example, in absence seizure, sensory cerebral cortex (SCX), ventrobasal posterior thalamic groups (VB), and reticular thalamic nucleus (RTN) are in an oscillatory loop in which RTN neurons are hyperpolarized and burst-fire through de-inactivation of T-type channels.…”