Mechanisms of PIEZO Channel Inactivation

Abstract

PIEZO channels PIEZO1 and PIEZO2 are the newly identified mechanosensitive, non-selective cation channels permeable to Ca2+. In higher vertebrates, PIEZO1 is expressed ubiquitously in most tissues and cells while PIEZO2 is expressed more specifically in the peripheral sensory neurons. PIEZO channels contribute to a wide range of biological behaviors and developmental processes, therefore driving significant attention in the effort to understand their molecular properties. One prominent property of PIEZO channels is their rapid inactivation, which manifests itself as a decrease in channel open probability in the presence of a sustained mechanical stimulus. The lack of the PIEZO channel inactivation is linked to various mechanopathologies emphasizing the significance of studying this PIEZO channel property and the factors affecting it. In the present review, we discuss the mechanisms underlying the PIEZO channel inactivation, its modulation by the interaction of the channels with lipids and/or proteins, and how the changes in PIEZO inactivation by the channel mutations can cause a variety of diseases in animals and humans.

Mechanosensitive receptors in migraine: a systematic review

“…Piezo1/2 channels are mechanically sensitive gigantic non-selective cationic ion channels, which are highly calcium permeable [ 42 ]. Our knowledge on functions of these recently discovered Piezo channels is actively updating [ 43 ]. Interestingly, Piezo1 was involved in mediating the reduction of pain threshold caused by sleep deprivation, while microinjection of the Piezo1 antagonist GSMTx4 partially reversed the pain threshold [ 44 ].…”

Application of TELC model to neuroscience: Better elucidation for neural stimulation by touch

“…Membrane potential response has been recorded from a Neuro2A (N2A) cell under current clamp to mechanical stimulation of PIZEO generated by depressing a glass probe against the cellular membrane 15 . Although much of the structural and mechanistic principles underlying Piezo gating and its general roles in physiology have been well elucidated through more than a decade of intense research, wide gaps of knowledge continue to exist 16,17,18 . For example, exactly how the transient ion transport activity of touch receptors could stimulate the firing of action potential spikes at certain bioenergetics physical chemistry level seems still not entirely clear.…”