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Effects of Osmolarity on Ultrasound-Induced Membrane Depolarization in Isolated Crayfish Motor Axon

Feiyuan Yu, Wolfgang S. Müller, Gösta Ehnholm, Yoshio Okada, Jen-Wei Lin

Ultrasound in Medicine & Biology 2022 · 10.1016/j.ultrasmedbio.2022.05.028

ex vivo tissuehealthyinvasive electrophysiology

Abstract

We have previously identified a novel non-selective membrane conductance (g US ) opened by focused ultrasound (FUS) in crayfish motor axons. In the work described here, we studied g US properties further by comparing FUS-evoked depolarization (FUSD) in control and hypotonic saline with 75% of control osmolarity. The FUS was a train of 20 FUS bursts (2.1 MHz and 50 µs per burst) delivered at 1 kHz. The amplitude, onset latency, frequency of occurrence and duration of FUSD were compared in a 15-min time window before and after switching to hypotonic saline. Significant increases were observed for amplitude (p US is mediated by opening of nanopores in the lipid bilayer and that stretching of axonal membrane caused by swelling at low osmolarity should increase the probability of nanopore formation under FUS. The FUSD parameters, in addition, exhibited time-dependent trends when the window of observation was expanded to 45 min in each saline. The statistical significance of amplitude and duration differed between 15- and 45-min time windows, indicating the presence of adaptive responses of axonal membrane to osmotic manipulation.

Abstract via europepmc.

SpeciesProcambarus clarkii (crayfish)
Subjects8 preparations
Sessions per subjectnot applicable
Randomisednot applicable
Blindingnot applicable
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutsinvasive electrophysiologyTwo-electrode current-clamp recording of FUS-evoked membrane depolarization (FUSD: amplitude, onset delay, frequency of occurrence, duration) in isolated crayfish opener motor axons
Direction of effectexcitatoryFUS tone-burst trains produced membrane depolarization (FUSD) in crayfish motor axons. Lowering saline osmolarity to 75% of control significantly increased FUSD amplitude and frequency of occurrence and shortened onset delay during a 15-min window after the switch, while FUSD duration was unchanged in that window (though it became significantly shorter over an expanded 45-min window).
Adverse eventsnot applicable

Exposures

Exposure 1: FUS tone-burst train applied to isolated motor axon

Target: excised nerve — “the motor axons of the crayfish opener neuromuscular junction
Device: custom-built · Steminc Piezo (Steiner & Martins) · SMSF20C30F21

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)2,100✓✓
Pulse duration (ms)0.05✓✓
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓
Sonication duration (s)0.02✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)100, 300swept✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)0.00094✓✓
In-situ estimatenot applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Protocol, in the paper’s words

A test current step to trigger action potentials was alternated with a trial testing the effect of the FUS tone burst; the time gap between the current step and the FUS tone burst was 0.5 s, FUSD was recorded as a 20-s-long trace, and there was a 10-s gap before the next test current step. The lowest FUS pressure capable of triggering FUSD in 10% of trials was chosen for each preparation.

Flags from extraction

  • exposures[0].timing.pulse_duration_msThe Methods text states 'each pulse lasting 50 ms', which conflicts with the abstract and Fig. 1D legend ('50 μs per burst'/'50-μs tone bursts') and with the stated duty cycle: 5% duty cycle at a 1 kHz PRF (1 ms period) implies a 50 μs pulse, not 50 ms. This is very likely an OCR/typographic confusion of μ for m. Recorded as 0.05 ms (50 μs) per the abstract/figure and the burst-rule arithmetic; the conflicting 'each pulse lasting 50 ms' wording appears in the Methods body.
  • exposures[0].free_field.pressure_kpa,exposures[0].free_field.ispta_w_cm2The preparation is an isolated axon bathed directly in saline with no skull or intervening tissue path; the paper does not use free-field/in-situ terminology. Values are placed in free_field per the instruction that in a bath/dish preparation with no skull or tissue path, in_situ is null.