(1) In short, Gene Ontology analysis has identified several potentially affected pathways involved in synaptic transmission (HTR2A, BDNF, CHRNA3, CHRNB4, DRD1, DRD2, DRD4, EGR1, GRIA4, GRIN2B, GRM3, NISCH, SLC1A3, and ERBB4), dopamine metabolic processes (COMT, DRD1, DRD2, DRD4, MAOA, NR4A2, and SLC6A3), and ion channel activity (CHRNA7, CACNA1I, CACNB2, CHRNA3, CHRNA5, CHRNB4, GABRB3, GRIA4, GRIA1, GRIN2B, HCN1, CACNA1C
, KCTD13, KCNV1, KCNN3, KCNJ13, and KCNB1).
Con base en los resultados reportados para el gen CACNA1C
por otros grupos que estudian la genetica del trastorno bipolar (Ferreira et al., 2008; Sklar et al., 2008; Liu et al., 2011), Gonzalez y colaboradores (2013) utilizaron una estrategia basada en familias latinas (incluyendo 38 familias costarricenses) para detectar asociacion con variantes en este gen.
In the first part of the project we will investigate the effects of genetic changes in VGCCs (especially in a gene called CACNA1C
) on the brain using rodent models.
CalbindinD28k, NM_031984.1, UPL Probe #128 (Roche 04693647001); Parvalbumin, NM_022499.1, UPL Probe #49 (Roche 04688104001); Grin1 NM_001270602.1 UPL Probe #69 (Roche 04688686001); Grin2a NM_012573.3 UPL Probe #66 (Roche 04688651001); Grin2b NM_012574.1 UPL Probe # 29 (Roche 04687612001); Grin2c NM_012575.3 UPL Probe #106 (Roche 04692250001); Grin2d NM_022797.1 UPL Probe #4 (Roche 04685016001); Grin3a NM_001198583.1 UPL Probe #105 (Roche 04692241001) CACNA1C
, NM_012517.2, UPL Probe #73 (Roche 04688961001); CACNA1D, NM_017298.1, UPL Probe #82 (Roche 04689054001).
(Cav1.2) in the pathophysiology of psychiatric disease.
A large number of imaging genetics studies have found that genetic mutation has an impact on the brain structure of schizophrenia, including gray matter volume (ACNA1C, NRGN, TCF4, and ZNF804A), ventricle volume (TCF4), cerebral cortex folds (NCAN) and thickness (ZNF804A), white matter integrity (ANK3 and ZNF804A), white matter volume (CACNA1C
and ZNF804A), white matter density (ZNF804A), and so forth.
, an intron variant of CACNA1C
(rs79398153), and a missense mutation of ANK3 (N2643S) were confirmed being involved in BD [95, 96].
([Ca.sub.v]1.2) which mediates the generation of the pacemaker potential and action potential in the SAN was also modestly reduced in GK compared to control SAN.
Furthermore, the genetic studies show that schizophrenia and bipolar disorder share certain susceptibility genes, e.g., CACNA1C
, NT5C2, and CCDC68 .
Six other genes (CACNA1C
, CACNB2, SCN1B, KCNQ3, SCN3B, and HCN4) have been associated with BrS, but the prevalence of variants in these genes is yet unknown (6).
Neurogenetic advances have demonstrated some shared genes among schizophrenia, bipolar disorders, and major depressive disorder (such as the CACNA1C
Some studies showed that cervical SCI promote shortening of QT interval and increases in QT dispersion (Bartholdy et al., 2014; Saunders et al., 2015).The short QT interval shows uniformity in time and space in the ventricle, producing an exaggerated heterogeneity of repolarization, hastens recovery and reduced refractoriness in the ventricle (Patel et al., 2010).The ion channelopathies that cause SQTS (mutation in KCNH2, KCNQ1, KCNJ2 that encodes cardiac [K.sup.+] channel or mutation in CACNA1c
, CACNB2b that encodes cardiac [Ca.sup.2+] channel) not only abbreviate repolarization but they significantly increase dispersion of repolarization, thus creating the cellular basis for both the substrate and trigger necessary for the initiation of reentry (Patel et al., 2010).