[Paper Review] Initiation and blocking of the action potential in the axon in a weak ultrasonic field

Mikhail N. Shneider, Mikhail Pekker|arXiv (Cornell University)|Sep 23, 2013

Photoreceptor and optogenetics researchNeuroscience23 references1 citations

TL;DR

This study demonstrates that weak ultrasonic fields can redistribute voltage-gated sodium channels in the axon initial segment, lowering the action potential threshold and enabling spontaneous firing, while excessive redistribution can block signal propagation. Using the Hodgkin-Huxley model, it shows that non-thermal electroacoustic forces from ultrasound can induce these changes at intensities far below those causing cavitation or heating, suggesting potential for ultrasound-based neuromodulation and non-invasive anesthesia.

ABSTRACT

Abstract In this paper we analyzed the effect of ultrasound on the redistribution of the transmembrane ion channels in the initial segment of the myelinated axon of a neuron. It is shown on the basis of Hodgkin-Huxley model of axon, that redistribution of the density of transmembrane sodium channels may reduce the threshold of the action potential, up to its spontaneous initiation. At significant redistribution of sodium channels in membrane, the zones of rarefaction of thetransmembrane channels density are formed blocking the propagation of the action potential. It is shown that the intensity of ultrasound at which the effect of transmembrane channels redistribution becomes noticeable is significantly greater than the intensity at which cavitation and overheating due to the ultrasound absorption occurs. However, as shown on an example of squid axon, the forced resonant electroacoustic oscillations excited in the membrane by the longitudinal electric component of the microwave may result in the transmembrane channels redistribution without essential heating. The intensity of the microwave, which may cause a spontaneous excitation of the action potential or its blocking on many orders of magnitude lower than the intensity at which come into play the thermal effects. The blocking effect of the action potential can be used in anesthesia.

Motivation & Objective

• To investigate how weak ultrasonic fields affect ion channel distribution in the axon initial segment.
• To determine whether ultrasound can initiate or block action potentials without thermal effects.
• To explore the feasibility of using ultrasound for non-invasive neuromodulation and anesthesia.
• To analyze the role of the longitudinal electric component of ultrasound in inducing electroacoustic oscillations in neuronal membranes.

Proposed method

• The Hodgkin-Huxley model of the axon was used to simulate changes in transmembrane ion channel dynamics under ultrasound exposure.
• The model analyzed the redistribution of sodium channel density in the axon initial segment due to mechanical forces from ultrasound.
• The study evaluated the threshold for action potential initiation under varying sodium channel densities.
• It assessed the intensity thresholds for ultrasound-induced channel redistribution versus those causing thermal effects like cavitation and heating.
• Forced resonant electroacoustic oscillations in the membrane were modeled to explain non-thermal channel redistribution.
• The squid giant axon was used as a model system to estimate realistic intensity levels for observable effects.

Experimental results

Research questions

• RQ1 Can weak ultrasound fields induce redistribution of voltage-gated sodium channels in the axon initial segment?
• RQ2 At what ultrasound intensity does channel redistribution become significant compared to thermal effects?
• RQ3 Can ultrasound-induced channel redistribution lead to spontaneous action potential initiation?
• RQ4 Can excessive channel redistribution block action potential propagation?
• RQ5 Can non-thermal electroacoustic forces from ultrasound be harnessed for neuromodulation or anesthesia?

Key findings

• Redistribution of sodium channels in the axon initial segment can lower the threshold for action potential initiation, leading to spontaneous firing.
• Excessive redistribution creates zones of low channel density that block action potential propagation.
• The intensity of ultrasound required to induce channel redistribution is significantly lower than that causing cavitation or thermal damage.
• Forced electroacoustic oscillations in the membrane can redistribute channels without significant heating, enabling non-thermal neuromodulation.
• The threshold intensity for inducing action potential initiation or blockage is several orders of magnitude lower than thermal thresholds.
• The blocking effect of action potentials via channel redistribution suggests potential for ultrasound-based non-invasive anesthesia.