Chronic lithium treatment of B lymphoblasts from bipolar disorder patients reduces transient receptor potential channel 3 levels

Abstract

Chronic lithium treatment of B-lymphoblast cell lines (BLCLs) from bipolar-I disorder (BD-I) patients and healthy subjects ex vivo attenuates agonist-and thapsigargin-stimulated intracellular calcium (Ca 2 þ ) responses. As these findings suggest that chronic lithium treatment modifies receptor (ROCE) and/or store-operated Ca 2 þ entry (SOCE) mechanisms, we determined whether chronic lithium treatment of BLCLs modified the expression of two members of the transient receptor potential channels (TRPC1 & 3), which participate in ROCE/SOCE. Chronic lithium treatment significantly reduced BLCL TRPC3 immunoreactivity (repeated-measures ANOVA, P ¼ 0.00005), with interaction effects of diagnosis (P ¼ 0.037) and sex (P ¼ 0.040). The lithium-induced decrease was greatest in BLCLs from female BD-I patients compared with those from healthy females (À27%) and with vehicle-treated BLCLs from female BD-I patients (À33%). However, lithium treatment did not affect TRPC1 and 3 mRNA levels, and TRPC1 immunoreactivity. Downregulation of TRPC3 may be an important mechanism by which lithium ameliorates pathophysiological Ca 2 þ disturbances as observed in BD.

Stargazin involvement with bipolar disorder and response to lithium treatment

“…In addition, as Stargazin interacts directly with the AMPA receptor and enhances its activity [40,[56][57][58], the difference in expression levels of Stargazin between patients with BPD and healthy participants may be consistent with some evidence of glutamate dysfunction in psychiatric disorders [34,[59][60][61][62]. Overexpression of Stargazin (calcium channel g-2 subunit) in brains of patients with BPD may account for the elevated free, intracellular calcium ion (Ca 2 + ) concentrations observed in blood platelets and lymphocytes of patients, as it increases the expression of AMPA receptors in the postsynaptic membrane, leading to an increased Ca 2 + influx through the NMDA receptor or voltage-dependent channels, as well as an exaggerated response to glutamate stimulation and a greater degree of depolarization followed by increased excitability [63][64][65][66][67].…”

Disrupted in Schizophrenia 1 Modulates Medial Prefrontal Cortex Pyramidal Neuron Activity Through cAMP Regulation of Transient Receptor Potential C and Small-Conductance K+ Channels

“…Although there are not yet strong links between SK and TRPC channelopathies and psychiatric disease, both channels have been linked to schizophrenia and/or bipolar disease (45–49). Interestingly, antidepressants and phenothiazine antipsychotics have a high affinity for SK channels (50) and chronic lithium treatment alters TRPC channel expression (51). …”

Characterization of the transient receptor potential channels mediating lysophosphatidic acid-stimulated calcium mobilization in B lymphoblasts

“…Full-length cDNA-AJ421783, Splice Variant A-AJ549088, Splice Variant B-AJ549089, Splice Variant C-AJ549090); sense 5′-AAGGCCAAAAGCTGTGA AAA-3′ and antisense 5′-CACCCTCAGGTGGTCTTTGT-3′, with an expected product size of 363 bp. The TRPC6 transcript was amplified using the primer pairs as described by Andreopoulos et al (2004), and the expected size of the amplicon was 98 bp. Each 50 μL PCR reaction mixture contained 1X PCR buffer, 200 μM dNTPs, 0.8 μM of each primer pairs, 1.25 U Taq DNA polymerase (MBI Fermentas, Burlington, ON), and 1.5 mM MgCl 2 .…”