Ultrasound Stimulation Modulates Voltage-Gated Potassium Currents Associated With Action Potential Shape in Hippocampal CA1 Pyramidal Neurons
Zhengrong Lin, Xiaowei Huang, Wei Zhou, Wenjun Zhang, Yingzhe Liu, Tianyuan Bian, Lili Niu, Long Meng, Yanwu Guo
Frontiers in Pharmacology 2019, 10 · 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.
Abstract via europepmc.
Exposures
Exposure 1: Ultrasound stimulation of CA1 pyramidal neurons via SAW neuro-modulation chip
Target: CA1 — “hippocampal CA1 pyramidal neurons”
Device: custom-built · ultrasound neuro-modulation chip (surface acoustic wave / IDT device)
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 27,380, 8,700swept | ✓✓✓⚑ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | 100 | ✓?⚑ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not applicable | |
| In-situ pressure (kPa) | not applicable | |
| In-situ Isppa (W/cm²) | not applicable | |
| In-situ Ispta (W/cm²) | not applicable | |
| Isppa, domain unspecified (W/cm²) | 0.465 | ✓✓✓ |
Continuous radio frequency (RF) signals were generated by an arbitrary waveform generator, amplified, and applied to both IDTs to generate standing surface acoustic waves. Ultrasound stimulation for 30 s duration on pyramidal neurons caused a significant increment in outward potassium currents. A second chip with a lower resonant frequency of 8.7 MHz was also used with the same parameters and produced similar results, indicating frequency had little influence on the effect.
Consistency checks: f0 out of range.
Flags from extraction
exposures[0].fundamental_frequency_khz— Paper also reports a second chip at 8.7 MHz used with 'the same parameters' as a frequency comparison at the same target; combined into one exposure per frequency-sweep exception rather than a second exposure.n_subjects— Paper gives neuron counts per figure (e.g., n=12) but does not state the number of animals used; recorded as not_reported.exposures[0].timing.duty_cycle_pct— Continuous-wave RF signal stated explicitly; duty cycle set to 100 by convention for CW per the schema rule, not independently stated as a percentage in the text.