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Lewin, G. R.

Publications and source records attributed to Lewin, G. R..

2 recordsLinked to original sources

Specialized mechanoreceptor systems in rodent glabrous skin

Rodents use their forepaws to actively interact with their tactile environment. Studies on the physiology and anatomy of glabrous skin that makes up the majority of the forepaw are almost non-existent in the mouse. Here we developed a preparation to record from single sensory fibers of the forepaw and compared anatomical and physiological receptor properties to those of the hind paw glabrous and hairy skin. We found that the mouse forepaw skin is equipped with a very high density of mechanoreceptors; >3 fold more than hind paw glabrous skin. In addition, rapidly adapting mechanoreceptors that innervate Meissners corpuscles of the forepaw were several-fold more sensitive to slowly moving mechanical stimuli compared to their counterparts in the hind paw glabrous skin. All other mechanoreceptors types as well as myelinated nociceptors had physiological properties that were invariant regardless of which skin area they occupied. We discovered a novel D-hair receptor innervating a small group of hairs in the middle of the hind paw glabrous skin in mice. Glabrous D-hair receptors were direction sensitive albeit with an orientation sensitivity opposite to that described for hairy skin D-hair receptors. Glabrous D-hair receptors do not occur in all rodents, but are present in North American and African rodent species that diverged more than 65 million years ago. The function of these specialized hairs is unknown, but they are nevertheless evolutionarily very ancient. Our study reveals novel physiological specializations of mechanoreceptors in the glabrous skin that likely evolved to facilitate tactile exploration.

neuroscience

Voltage-gating of mechanosensitive PIEZO channels

Mechanosensitive PIEZO ion channels are evolutionarily conserved proteins whose presence is critical for normal physiology in multicellular organisms. Here we show that, in addition to mechanical stimuli, PIEZO channels are also powerfully modulated by voltage and can even switch to a purely voltage gated mode. Mutations that cause human diseases such as Xerocytosis profoundly shift voltage sensitivity of PIEZO1 channels towards the resting membrane potential and strongly promote pure voltage gating. Our data may be explained by the presence of an inactivation gate in the pore, the opening of which is promoted by outward permeation. Invertebrate (fly) and vertebrate (fish) PIEZO proteins are also voltage sensitive but voltage gating is a much more prominent feature of these older channels. We propose that the voltage sensitivity of PIEZO channels is a deep property co-opted to add a regulatory mechanism for PIEZO activation in widely different cellular contexts.

neuroscience