Thermal block of action potentials is primarily due to voltage-dependent potassium currents: a modeling study

Mohit Ganguly,E Duco Jansen,Hillel J Chiel,Michael W Jenkins

doi:10.1088/1741-2552/ab131b

Mohit Ganguly, E Duco Jansen + Show 2 more

Open Access

https://doi.org/10.1088/1741-2552/ab131b

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Abstract

Objective. Thermal block of action potential conduction using infrared lasers is a new modality for manipulating neural activity. It could be used for analysis of the nervous system and for therapeutic applications. We sought to understand the mechanisms of thermal block. Approach. To analyze the mechanisms of thermal block, we studied both the original Hodgkin/Huxley model, and a version modified to more accurately match experimental data on thermal responses in the squid giant axon. Main results. Both the original and modified models suggested that thermal block, especially at higher temperatures, is primarily due to a depolarization-activated hyperpolarization as increased temperature leads to faster activation of voltage-gated potassium ion channels. The minimum length needed to block an axon scaled with the square root of the axon’s diameter. Significance. The results suggest that voltage-dependent potassium ion channels play a major role in thermal block, and that relatively short lengths of axon could be thermally manipulated to selectively block fine, unmyelinated axons, such as C fibers, that carry pain and other sensory information.

Highlights

Targeted optical manipulation of the nervous system has become an exciting new possibility in recent years
Increasing temperature leads to a net increase in hyperpolarizing current We first determined whether adding temperature-dependence to components of the original Hodgkin/Huxley led to qualitatively new behavior, or primarily altered the quantitative response of the modified model to temperature
This is the first study to provide quantitative evidence for a mechanism of thermal block that was originally suggested by Huxley (1959): thermal block at higher temperatures is due primarily to activation of voltage-dependent potassium ion channels

Summary

Introduction

Targeted optical manipulation of the nervous system has become an exciting new possibility in recent years. The new field of infrared control of excitable tissue has been recently reviewed (Thompson et al 2014). Several possible mechanisms have been suggested for IR-induced excitation, including the induction of capacitive currents due to thermal gradients (Shapiro et al 2012, Plaksin et al 2017), activation of mitochondrial calcium currents (Dittami et al 2011, Lumbreras et al 2014), endoplasmic reticulum (Tolstykh et al 2017), and direct actions on ion channels (Albert et al 2012). It has been shown that infrared laser light can be used to inhibit both action potentials traveling through axons and through cardiomyocytes (Duke et al 2013, Lothet et al 2014, Wang et al 2016, Lothet et al 2017). Rather than inducing a thermal gradient, it appears that the inhibitory mechanism is due to raising tissue temperature (Duke et al 2013). Understanding the effects of temperature on axonal conduction could be very useful for more precisely designing ways of controlling neural activity

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