Repeated Electroconvulsive Shock Induces Changes in High-affinity [3H]-ouabain Binding to Rat Striatal Membranes

Abstract

Repeated electroconvulsive shock is an effective treatment for affective disorders. Striatum, hippocampus and brainstem are involved in affective disorders. Sodium-potassium/ATPase is of paramount importance for the proper functioning of the brain and its involvement in the affective disorders has been claimed for a long time. Sodium-potassium/ATPase has an extracellular regulatory binding site to which cardiotonic glycosides, such as ouabain, bind to, thus regulating the activity of the enzyme. Endogenous "ouabain-like" substances exist in the brain and their actions on the sodium-potassium/ATPase resemble ouabain biological properties. The aim of this work was to determine if electroconvulsive shock (ECS) would induce changes in the high-affinity binding of ouabain to the sodium-potassium/ATPase from rat brain regions. Adult, male Wistar rats received one (ECSx1 group) or seven electroshocks (ECSx7 group) delivered daily through ear-clips electrodes. Control rats received the same manipulations; however, no current was delivered through the electrodes (SHAMx1 and SHAMx7 groups). All groups were sacrificed 24 h after the last ECS session. The B (max) and K (D) of high-affinity [(3)H]-ouabain binding were determined in crude membrane preparations from the striatum, hippocampus and brainstem. The results obtained showed a statistically significant increase in the affinity of [(3)H]-ouabain (lower K (D)) to striatal membranes in those rats receiving seven ECS. In the striatum there was no change in the K (D) after one ECS; as well as there was no change in the B (max) after a single or seven ECS. High-affinity [(3)H]-ouabain binding to hippocampus and brainstem did not reveal any significant differences either in K (D) or B (max) after one or seven ECS. The increased affinity of ouabain to the striatal sodium-potassium/ATPase induced by repeated ECS suggests an increased interaction in vivo of the endogenous "ouabain-like" substances with the enzyme and the involvement of the extracellular regulatory allosteric ouabain binding site in the striatal sodium-potassium/ATPase in the effects of electroconvulsive shock.

Na, K-ATPase α3 is a death target of Alzheimer patient amyloid-β assembly

“…This concentration was 40% of the concentration of NAKα3 (35.2 ± 10 pmol/mg membrane protein; n = 4) that we measured (as shown in Fig. 3G using prequantified, cell-free synthesized NAKα3 as the quantification standard; for details see SI Materials and Methods) and it was ∼37-88% of the concentrations found in the literature (16-38 pmol/mg membrane protein) (33,34). Simple arithmetic calculations thus give an ASPD:NAKα3 ratio ranging from 1:1-1:3.…”

Neurotensin decreases high affinity [3H]-ouabain binding to cerebral cortex membranes

“…This finding may be related to the increased Kd value for high affinity [ 3 H]-ouabain binding to CNS membranes reported after sleep deprivation [31]. In support, a decrease in Kd value after neuronal hyperactivity induced by repeated electroconvulsive shock was observed [32]. On the other hand, antagonist SR 48692 modified Bmax but failed to alter Kd value (present results).…”