Activation of Piezo1 but Not NaV1.2 Channels by Ultrasound at 43 MHz

Prieto, Martin Loynaz; Firouzi, Kamyar; Khuri‐Yakub, Butrus T.; Maduke, Merritt

doi:10.1016/j.ultrasmedbio.2017.12.020

Cited by 127 publications

(139 citation statements)

References 68 publications

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“…Stimulation of stretch activated channels was proposed as the underlying mechanism. Interestingly, Piezo1 can be activated by ultrasound [35]. Though the significance of Piezo1 in physiological insulin secretion is not evident from our study, using mechanosensitive Piezo1 induction as a strategy to induce insulin secretion has clear clinical potential and warrants further investigation [34].…”

Section: Discussionmentioning

confidence: 78%

Piezo1 channel agonist mimics high glucose as a stimulator of insulin release

Deivasikamani

Dhayalan

Mughal

et al. 2018

Preprint

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Objective: Glucose and hypotonicity induced cell swelling stimulate insulin release from pancreatic b-cells but the mechanisms are poorly understood. Recently, Piezo1 was identified as a mechanically-activated nonselective Ca 2+ permeable cationic channel in a range of mammalian cells. As cell swelling induced insulin release could be through stimulation of Ca 2+ permeable stretch activated channels, we hypothesised a role for Piezo1 in cell swelling induced insulin release. Methods:Two rat b-cell lines (INS-1 and BRIN-BD11) and freshly-isolated mouse pancreatic islets were studied. Intracellular Ca 2+ measurements were performed using the fura-2 Ca 2+ indicator dye. Piezo1 agonist Yoda1, a competitive antagonist of Yoda1 (Dooku1) and an inactive analogue of Yoda1 (2e) were used as chemical probes. Piezo1 mRNA and insulin secretion were measured by RT-PCR and ELISA respectively.Results: Piezo1 mRNA was detected in both b-cell lines and mouse islets. Yoda1 evoked Ca 2+ entry which was inhibited by Yoda1 antagonist Dooku1 as well as other Piezo1 inhibitors gadolinium and ruthenium red, and not mimicked by 2e. Yoda1, but not 2e, stimulated Dooku1-sensitive insulin release from b-cells and pancreatic islets. Hypotonicity and high glucose increased intracellular Ca 2+ and enhanced Yoda1 Ca 2+ influx responses. Pre-treatment with ruthenium red significantly reduced hypotonicity induced insulin release from b-cells and pancreatic islets. Conclusion:The data show that Piezo1 channel agonist induces insulin release from b-cell lines and mouse pancreatic islets suggesting a role for Piezo1 in cell swelling induced insulin release. Hence Piezo1 agonists have a potential to be used as enhancers of insulin release.

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Section: Discussionmentioning

confidence: 78%

Piezo1 channel agonist mimics high glucose as a stimulator of insulin release

Deivasikamani

Dhayalan

Mughal

et al. 2018

Preprint

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“…This possibility is likely given the emerging view that the e↵ects of ultrasound on neurons are of a mechanical kind. In particular, the mechanical forces associated with propagating ultrasound displace membranes and this way open mechanosensitive ion channels (Tyler, 2011;Kubanek et al, 2018;Prieto et al, 2018). It has been demonstrated that such mechanosensing molecules adapt to repetitive mechanical stimulation (Ge↵eney and Goodman, 2012).…”

Section: Discussionmentioning

confidence: 99%

Transcranial ultrasound selectively biases decision-making in primates

Kubanek¹,

Brown²,

Ye³

et al. 2018

Preprint

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Transcranial focused ultrasound has the promise to evolve into a transformative noninvasive way to modulate activity of neuronal circuits deep in the brain. The approach may enable systematic and causal mapping of how individual brain circuits are involved in specific behaviors and behavioral disorders. Previous studies demonstrated neuromodulatory potential, but the e↵ect polarity, size, and spatial specificity have been di cult to assess. Here, we engaged non-human primates (macaca mulatta) in an established task that provides a well defined framework to characterize the neuromodulatory e↵ects. In this task, subjects decide whether to look at a right or a left target, guided by one the targets appearing first. Previous studies showed that excitation/inhibition of oculomotor circuits leads to contralateral/ipsilateral biases in this choice behavior. We found that brief, low-intensity ultrasound stimuli (300 ms, 0.6 MPa, 270 kHz) delivered to the animals' left/right frontal eye fields bias the animals' decisions to the right/left visual hemifield. The e↵ect was modest, about on the order of that produced when injecting moderate amounts of potent neuromodulatory drugs into the same regions in this task. The polarity of the e↵ects suggested a neuronal excitation within the stimulated regions. No e↵ects were observed when we applied the same stimuli to control brain regions not involved in oculomotor target selection. Together, using an established paradigm, we found that transcranial ultrasound is capable of modulating neurons to the extent of biasing choice behavior of non-human primates. A demonstration of tangible, brain-region-specific e↵ects on behavior of primates constitutes a critical step toward applying this noninvasive neuromodulation method in investigations of how specific neural circuits are involved in specific behaviors or disease signs. Sato et al., 2018). In these studies, applications of low-intensity stimuli to peri-motor regions often lead to visible movements of the limbs or other body parts. There have been concerns that the small size of the rodent brain, relative to the dimensions of the focal spot, results in reflections, Li

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“…Despite this theoretical model, and the work in small animal models, the effect of tFUS parameters on neuronal excitation in humans is not well understood empirically and indeed the basic putative mechanisms of how mechanical energy affects neuronal excitability is still largely theoretical [28][29][30][31]. There is evidence for US to affect certain mechanosensitive channels [32,33] but the proliferation and density of these channels in human CNS is not well understood and the contribution of these channels to pyramidal excitation and neurovascular coupling is also unclear.…”

Section: Discussionmentioning

confidence: 99%

Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI

Bansal

Mueller

et al. 2018

Preprint

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Background: Transcranial focused ultrasound (tFUS) is a new non-invasive neuromodulation technique that uses mechanical energy to modulate neuronal excitability with high spatial precision. tFUS has been shown to be capable of modulating EEG brain activity in humans that is spatially restricted, and here, we use 7T MRI to extend these findings. We test the effect of tFUS on 7T BOLD fMRI signals from individual finger representations in the human primary motor cortex (M1) and connected cortical motor regions. Participants (N = 5) performed a cued finger tapping task in a 7T MRI scanner with their thumb, index, and middle fingers to produce a BOLD signal for individual M1 finger representations during either tFUS or sham neuromodulation to the thumb representation.Results: Results demonstrated a statistically significant increase in activation volume of the M1 thumb representation for the tFUS condition as compared to sham. No differences in percent BOLD changes were found. This effect was spatially confined as the index and middle finger M1 finger representations did not show similar significant changes in either percent change or activation volume. No effects were seen during tFUS to M1 in the supplementary motor area (SMA) or the dorsal premotor cortex (PMd). Conclusions:Single element tFUS can be paired with high field MRI that does not induce significant artifact. tFUS increases activation volumes of the targeted finger representation that is spatially restricted within M1 but does not extend to functionally connected motor regions.

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Activation of Piezo1 but Not NaV1.2 Channels by Ultrasound at 43 MHz

Cited by 127 publications

References 68 publications

Piezo1 channel agonist mimics high glucose as a stimulator of insulin release

Piezo1 channel agonist mimics high glucose as a stimulator of insulin release

Transcranial ultrasound selectively biases decision-making in primates

Effects of transcranial focused ultrasound on human primary motor cortex using 7T fMRI

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