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 Ca2 + 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) Ca2 + concentrations modulate the electrodynamic properties of MTs. Electrical amplification by MTs was exponentially dependent on the Ca2 + concentration between 10 − 7 and 10 − 2 M. However, the electrical connectivity (coupling) of MTs was optimal at a narrower window of Ca2 + concentrations. We observed that while raising bathing Ca2 + concentration increased electrical amplification by MTs, energy transfer was highest in the presence of ethylene glycol tetraacetic acid (lowest Ca2 + concentration). Our data indicate that Ca2 + 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 Ca2 + -dependent ability of MTs to modulate and amplify electrical signals may provide a novel means of cell signaling, likely contributing to neuronal function.
This is a preview of subscription content, log in to check access.
Funding from NSERC (Canada), MITACS and Technology Innovations, LLC of Rochester, NY, USA supported this research (AP & JT). HC was partially funded by the PKD Foundation. AJR is the recipient of a PKD Foundation postdoctoral fellowship.
Regehr, W.G., Tank, D.W.: Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal pyramidal cells. J. Neurosci. 12(11), 4202–4223 (1992)Google Scholar
Zarkovic, M., Henquin, J.C.: Synchronization and entrainment of cytoplasmic Ca2 + oscillations in cell clusters prepared from single or multiple mouse pancreatic islets. Am. J. Physiol. Endocrinol. Metab. 287, E340–E347 (2004). doi:10.1152/ajpendo.00069.2004CrossRefGoogle Scholar
Hallaq, H.A., Haupert Jr., G.T.: Positive inotropic effects of the endogenous Na + /K + -transporting ATPase inhibitor from the hypothalamus. Proc. Natl. Acad. Sci. USA 86, 10080–10084 (1989). doi:10.1073/pnas.86.24.10080CrossRefADSGoogle Scholar
Karr, T.L., Kristofferson, D., Purich, D.L.: Calcium ion induces endwise depolymerization of bovine brain microtubules. J. Biol. Chem. 255, 11853–11856 (1980)Google Scholar
Astier, Y., Bayley, H., Howorka, S.: Protein components for nanodevices. Curr. Opin. Chem. Biol. 9, 576–584 (2005)Google Scholar
Vizcarra, C.L., Mayo, S.L.: Electrostatics in computational protein design. Curr. Opin. Chem. Biol. 9, 622–626 (2005)Google Scholar
Sheetz, M.P., Steuer, E.R., Schroer, T.A.: The mechanism and regulation of fast axonal transport. Trends Pharmacol. Sci. 12, 474–478 (1989)Google Scholar
Baas, P.W., Deitch, J.S., Black, M.M., Banker, G.A.: Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite. Proc. Natl. Acad. Sci. USA 85, 8335–8339 (1988). doi:10.1073/pnas.85.21.8335CrossRefADSGoogle Scholar
Brady, S.T., Lasek, R.J., Allen, R.D.: Video microscopy of fast axonal transport in extruded axoplasm: a new model for study of molecular mechanisms. Cell Motil. 5, 81–101 (1985). doi:10.1002/cm.970050203CrossRefGoogle Scholar