Inhibitory effect of ultrasonic stimulation on the voltage-dependent potassium currents in rat hippocampal CA1 neurons
Kun Cui, Shuai Zhang, Jinyao Sun, Xueying Zhang, Chong Ding, Guizhi Xu
BMC Neuroscience 2019, 20 · 10.1186/s12868-018-0485-1
Abstract
Background Transcranial ultrasonic stimulation is a novel noninvasive tool for neuromodulation, and has high spatial resolution and deep penetration. Although it can increase excitation of neurons, its effects on neuron are poorly understood. This study was to evaluate effect of ultrasonic stimulation (US) on neurons in vitro. In this paper, the effect of US on the excitability and voltage-dependent [Formula: see text] currents of CA1 pyramidal neurons in the rat hippocampus was studied using patch clamp. Results Our results suggest that US increased the spontaneous firing rate and inhibited transient outward potassium current ([Formula: see text]) and delayed rectifier potassium current ([Formula: see text]. Furthermore, US altered the activation of [Formula: see text] channels, inactivation and recovery properties of [Formula: see text] channels. After US, the [Formula: see text] activation curves significantly moved to the negative voltage direction and increased its slope factor. Moreover, the data showed that US moved the inactivation curve of [Formula: see text] to the negative voltage and increased the slope factor. Besides, US delayed the recovery of [Formula: see text] channel. Conclusions Our data indicate that US can increase excitation of neurons by inhibiting potassium currents. Different US decreased the voltage sensitivity of [Formula: see text] activation differentially. Moreover, the more time is needed for US to make the [Formula: see text] channels open again after inactivating. US may play a physiological role by inhibiting voltage-dependent potassium currents in neuromodulation. Our research can provide a theoretical basis for the future clinical application of ultrasound in neuromodulation.
Abstract via europepmc.
Exposures
Exposure 1: Ultrasonic stimulation of hippocampal CA1 brain slices
Target: CA1 — “rat hippocampal CA1 neurons”
Device: Olympus / Panametrics · Olympus · V308 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 20 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 40%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 900 | ✓✓✓ |
| 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) | 0.015, 0.03swept | ✓✓✓⚑ |
The ultrasound settings were 0.5 MHz center frequency, 20 Hz pulse repetition frequency, 50% duty cycle and 20 ms pulse length, and the pulse-average ultrasound intensities were 15 mW/cm2 or 30 mW/cm2. All stimulations lasted 15 min. The transducer (diameter 24 mm) was immersed in aCSF 1.5 cm above the brain slice and stimulated the entire slice.
Flags from extraction
sham_type— Control condition was brain slices with no stimulation applied; the paper does not describe whether an inactive transducer was left in place, so the sham mechanism is not fully described.exposures[0].timing.pulse_duration_ms— Stated pulse length (20 ms) does not exactly match duty_cycle/PRF (50%/20 Hz = 25 ms); recorded as stated, not corrected.exposures[0].unspecified_domain.isppa_w_cm2— Paper reports 'pulse-average ultrasound intensity' without stating whether this was measured in water/free field or at the slice; placed in unspecified_domain.readout_timing— Paper does not state whether patch-clamp recordings were made during or after the 15-minute ultrasound exposure.