Electrical characterization of the oscillations observed in microtubule sheets in the presence of lithium

GUTIERREZ, BRENDA CELESTE; CANTIELLO, HORACIO F.; CANTERO, MARÍA DEL ROCÍO

CÓRDOBA

Congreso; LI Reunión Anual de la Sociedad Argentina de Biofísica; 2023

SAB

Lithium is a cation with a recognized mood-stabilizing effect in treating bipolar disorderand mania. Lithium is known to affect cellular function by inhibiting the metabolism ofinositol phospholipids, affecting signal transduction. However, there needs to be acomplete explanation of the mechanism of action by which lithium would exert itstherapeutic action. Different lithium compounds have recently been reported to affectelectroencephalogram (EEG) waves in rat brains (Konenkov, 2018). In the last ten years inour laboratory, we have shown that microtubules obtained from bovine and murine brainsgenerate and sustain electrical oscillations with characteristic fundamental frequenciesthat can be decomposed into waves similar to those observed in the human EEG. In thepresent study, we explored the possibility that lithium is transported by the nanopores inmicrotubules (MTs). We used the patch-clamp technique to seal brain MT sheets with 200mM LiCl in the pipette and the bath solutions and recorded the electrical activity. Weobserved the presence of sustained oscillations as previously reported with other cations(Cantero, 2016; 2018), but with fundamental frequencies of around 38 Hz and 77 Hz.Current-to-voltage relationships showed a mean conductance of 14.0 ± 1.9 nS (n = 3). Inthe presence of 140 mM KCl in the pipette and the bath, the addition of LiCl shifted thepeak of the fundamental frequency. These results show that lithium is transportedthrough the wall of the MTs, producing oscillatory currents with defined fundamentalfrequencies that differ from those observed with intracellular cations such as potassium.The evidence suggests that lithium transport by the MTs may modify a novel intracellularsignaling mechanism that contributes to its pharmacological effect in brain signaltransmission.