Microtubules (MTs) are important cytoskeletal superstructures implicated in neuronal morphology and function, which are involved in vesicle trafficking, neurite formation and differentiation and other morphological changes. The structural and functional properties of MTs depend on their high intrinsic charge density and functional regulation by the MT depolymerising properties of changes in Ca(2 + ) concentration. Recently, we reported on remarkable properties of isolated MTs, which behave as biomolecular transistors capable of amplifying electrical signals (Priel et al., Biophys J 90:4639-4643, 2006). Here, we demonstrate that MT-bathing (cytoplasmic) Ca(2 + ) concentrations modulate the electrodynamic properties of MTs. Electrical amplification by MTs was exponentially dependent on the Ca(2 + ) concentration between 10( - 7) and 10( - 2) M. However, the electrical connectivity (coupling) of MTs was optimal at a narrower window of Ca(2 + ) concentrations. We observed that while raising bathing Ca(2 + ) concentration increased electrical amplification by MTs, energy transfer was highest in the presence of ethylene glycol tetraacetic acid (lowest Ca(2 + ) concentration). Our data indicate that Ca(2 + ) is an important modulator of electrical amplification by MTs, supporting the hypothesis that this divalent cation, which adsorbs onto the polymer's surface, plays an important role as a regulator of the electrical properties of MTs. The Ca(2 + )-dependent ability of MTs to modulate and amplify electrical signals may provide a novel means of cell signaling, likely contributing to neuronal function.