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Related Concept Videos

Mechanically-gated Ion Channels01:12

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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
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  11. Piezo2 Voltage-block Regulates Mechanical Pain Sensitivity

Piezo2 voltage-block regulates mechanical pain sensitivity

Oscar Sánchez-Carranza1, Sampurna Chakrabarti1, Johannes Kühnemund1

  • 1Molecular Physiology of Somatic Sensation Laboratory, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin 10409, Germany.

Brain : a Journal of Neurology
|July 10, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Altering PIEZO2 ion channel voltage sensitivity in mice surprisingly sensitized pain-sensing neurons, leading to hypersensitivity to mechanical stimuli. This suggests relieving PIEZO2 voltage block may drive chronic pain conditions.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Physiology

Background:

  • PIEZO2 is a mechanically-gated ion channel crucial for touch sensation in sensory neurons.
  • PIEZO2 channels are voltage-modulated, being blocked at negative resting potentials and available at positive voltages.
  • The physiological role of PIEZO2's voltage sensitivity in sensory perception remained largely unknown.

Purpose of the Study:

  • To investigate the physiological consequences of altered PIEZO2 voltage sensitivity in vivo.
  • To characterize the biophysical properties and in vivo function of PIEZO2 mutations affecting voltage sensitivity.

Main Methods:

  • Generated Piezo2R2756H/R2756H and Piezo2R2756K/R2756K knock-in mice via genome engineering.
  • Measured mechanosensitive currents in dorsal root ganglia sensory neurons using electrophysiology.
Keywords:
human developmental disordersion channelsmechanotransductionpain

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  • Assessed mechanoreceptor and nociceptor function, and performed behavioral and morphological analyses in mice.

    • Main Results:

    • PIEZO2 mutations at R2756 relieved voltage block and lowered mechanical activation thresholds.
    • Knock-in mice exhibited sensitized mechanosensitive currents in nociceptors, but only mildly affected touch mechanoreceptors.
    • Cutaneous nociceptors in knock-in mice became ultrasensitive to mechanical stimuli, showing enhanced ongoing activity and behavioral hypersensitivity.

    Conclusions:

    • Relieving PIEZO2 voltage block can drive nociceptor sensitization and ongoing activity, mimicking phenomena in chronic pain.
    • Altered PIEZO2 voltage sensitivity in nociceptors, not touch mechanoreceptors, underlies mechanical hypersensitivity.
    • PIEZO2 ion channel function is critical for distinguishing noxious from non-noxious mechanical stimuli.
    voltage-block