Electrical Oscillations of Isolated Brain Microtubules

Abstract

Significance Statement. Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities. Recent in vitro electrophysiological studies indicate that different brain MT structures, including two-dimensional sheets and bundles, generate highly synchronous electrical oscillations. However, no information has been heretofore available as to whether isolated MTs also engage in electrical oscillations. In the present study, a broader spectrum of fundamental frequencies was always observed in isolated MTs as compared to the MT sheets. This interesting finding is consistent with the possibility that more structured MT complexes (i.e. bundles, sheets) may render more coherent response at given oscillatory frequencies and raise the hypothesis that combined MTs may tend to oscillate and entrain together. The present study provides to our knowledge the first experimental evidence for electrical oscillations of single brain MTs.Abstract. Microtubules (MTs) are important cytoskeletal structures engaged in a number of specific cellular activities, including vesicular traffic and motility, cell division, and information transfer within neuronal processes. MTs also are highly charged polyelectrolytes. Recent in vitro electrophysiological studies indicate that different brain MT structures, including two-dimensional (2D) sheets (MT sheets) and bundles, generate highly synchronous electrical oscillations. However, no information has been heretofore available as to whether isolated MTs also engage in electrical oscillations, despite the fact that taxol-stabilized isolated MTs are capable of amplifying electrical signals. Herein we tested the effect of voltage clamping on the electrical properties of isolated non-taxol stabilized brain MTs. Electrical oscillations were observed on application of holding potentials between ±200 mV that responded accordingly with changes in amplitude and polarity. Frequency domain spectral analysis of time records from isolated MTs disclosed a richer oscillatory response as compared to that observed in voltage clamped MT sheets from the same preparation. The data indicate that isolated brain MTs are electrical oscillators that behave as "ionic-based" transistors whose activity may be synchronized in higher MT structures. The ability of MTs to generate, propagate, and amplify electrical signals may have important implications in neuronal computational capabilities.

The Electrical Analogue Computer of Microtubule’s Protofilament

“…By decreasing the value R ′ as R ′ ≤ 1KΩ (Figures 8 and 9), the output voltages exhibit a decreasing behaviour of the oscillation amplitude over time, without becoming linear similar to the behaviour shown in Figures 3 and 4). Results obtained in Figures 8 and 9 are similar to those obtained by Gutierrez et al [21]. By decreasing the values of R 3 and R 5 as shown in Figure 9, the same behaviour as in Figure 8 is obtained.…”

“…For R ′ ≻10 KΩ as shown in Figure 7, the oscillations collapse over time and the output voltages become linear. In fact, by increasing the value of R ′ up to 10 KΩ, the output voltages also exhibit two regimes: spontaneous amplification of oscillations from 0 s until 0.8 s with a clear change in the signal's amplitude and then a constant and linear response from 0.8 s until 2 s. ese changes in regime and amplitude can suggest changes in polarity of the holding potential and conductance as reported by Gutierrez et al [21] in the case of isolated microtubule.…”

“…is situation puts forward realistic behaviour of the physical system as previously mentioned. Spontaneous changes are well observed in signal's amplitude, suggesting that intracellular electrical signaling may heavily obey to the assembly and organization of the various cytoskeletal structures over time [21]. For R ′ ≻10 KΩ as shown in Figure 7, the oscillations collapse over time and the output voltages become linear.…”

“…ey reported that MTs behave as biomolecular transistors capable of amplifying electrical information [8]. Recently, Gutierrez et al reported that isolated brain MTs are electrical oscillators that behave as "ionic-based" transistors and amplify electrical signals which may have important implications in neuronal computational capabilities [21]. All the abovementioned studies have been done experimentally.…”

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“…Interestingly, mean currents were often linear respect to voltage, although spontaneous changes in amplitude of the cyclic regimes were observed as well. Although similar, the oscillatory response of the bundles was richer than that reported for brain MT sheets 5 and more coherent than that observed in isolated MTs 6 . Thus, the geometry of the MT assembly may be an important factor in the nonlinear electrical outcome.…”