Ultrasound Stimulation Modulates Voltage-Gated Potassium Currents Associated With Action Potential Shape in Hippocampal CA1 Pyramidal Neurons.

Zhengrong Lin,Xiaowei Huang,Long Meng,Wei Zhou,Tianyuan Bian,Wenjun Zhang,Yanwu Guo,Lili Niu,Yingzhe Liu

doi:10.3389/fphar.2019.00544

Abstract

Potassium channels (K+) play an important role in the regulation of cellular signaling. Dysfunction of potassium channels is associated with several severe ion channels diseases, such as long QT syndrome, episodic ataxia and epilepsy. Ultrasound stimulation has proven to be an effective non-invasive tool for the modulation of ion channels and neural activity. In this study, we demonstrate that ultrasound stimulation enables to modulate the potassium currents and has an impact on the shape modulation of action potentials (AP) in the hippocampal pyramidal neurons using whole-cell patch-clamp recordings in vitro. The results show that outward potassium currents in neurons increase significantly, approximately 13%, in response to 30 s ultrasound stimulation. Simultaneously, the increasing outward potassium currents directly decrease the resting membrane potential (RMP) from −64.67 ± 1.10 mV to −67.51 ± 1.35 mV. Moreover, the threshold current and AP fall rate increase while the reduction of AP half-width and after-hyperpolarization peak time is detected. During ultrasound stimulation, reduction of the membrane input resistance of pyramidal neurons can be found and shorter membrane time constant is achieved. Additionally, we verify that the regulation of potassium currents and shape of action potential is mainly due to the mechanical effects induced by ultrasound. Therefore, ultrasound stimulation may offer an alternative tool to treat some ion channels diseases related to potassium channels.

Highlights

Potassium channels (K+), a high degree of diversity and ubiquity embedded within cellular membranes of neurons, are one of the most fundamental and important component in the function of ion channels (Mackinnon, 2003; Mckeown et al, 2008; Coetzee et al, 2010)
Compared to the control group, ultrasound stimulation for 30 s duration on pyramidal neurons caused a significant increment in the peak amplitude of outward potassium currents, approximately 13% (Figures 2A–C)
The results demonstrated that ultrasound stimulation was capable of modulating the potassium channels directly

Summary

Introduction

Potassium channels (K+), a high degree of diversity and ubiquity embedded within cellular membranes of neurons, are one of the most fundamental and important component in the function of ion channels (Mackinnon, 2003; Mckeown et al, 2008; Coetzee et al, 2010). Functional modulation of potassium channels is of great significance for clinical treatment of these relevant diseases (Lawson, 2000b; Maljevic and Lerche, 2013). Various studies have demonstrated that regulation of neuronal activity induced by ultrasound stimulation resulted from activating ion channels with different types (Bystritsky et al, 2011). Tyler et al (2008) illustrated that ultrasound could induce electrical activity in neurons by activating voltage-gated sodium channels and voltage-gated calcium channels. Kubanek et al (2016) showed that ultrasound stimulation could directly modulate the trans-membrane currents flowing through the mechanosensitive ion channels (sodium channels and potassium channels) expressed in Xenopus oocytes. We reported that ultrasound stimulation enables to increase neuronal excitability by increasing the total sodium currents and modulating the sodium channels kinetics (Lin et al, 2018)

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Conclusion