An investigation using cultured human cell lines, of the involvement of vanadium, cation transport and phosphatidylinositol in the aetiology of bipolar manic-depressive psychosis

Abstract

The symptoms, classification, occurrence and possible aetiologies of bipolar manic-depressive psychosis have been reviewed, with particular emphasis on the possible role of the vanadate ion (V5+) and cation transport in the illness. The effect of vanadate on cation transport in intact cells has been determined using the well-characterised HeLa cell line. Cation transport in virally transformed lymphoblastoid cell lines from 13 bipolar manic-depressive patients and 13 control subjects has been examined, under normal conditions and after treatment (24 hours) with lithium, ouabain or vanadate. The phosphatidylinositol system has also been examined in these cell lines, in view of the therapeutic effect of lithium, and its known inhibitory actions on inositol I-phosphatase. In HeLa cells, no effects of vanadate on cation transport were seen until concentrations greater than 3.2 x 10- 6 M. This was attributed to the intracellular reduction of V5+ to V4+ shown to occur using ESR. Similar decreases were seen in all the K+ influx pathways, with maximum decreases of approximately 30% at 10-4M vanadate extracellularly. Significant toxicity was also seen at these concentrations, with a maximum decrease in cell number of 40% at 10-4M vanadate. No change in the energy charge was seen and changes in ATP levels occurred subsequently to the changes in cell number, with a decrease of 40% at 10-4M vanadate. Using the lymphoblastoid cell lines, no significant differences were seen in any of the cation transport parameters examined, with the exception of mean sodium pump number which was 30% greater in the bipolar group compared with the control group. Lithium or vanadate treatment produced either no effect or inconsistent changes in cation transport. Ouabain treatment produced similar decreases in sodium pump number in both groups. Inositol uptake was similar in both groups, but the percentage incorporation into phosphoinositides was reduced in bipolar cell lines compared with controls.