Osmoregulatory inositol transporter SMIT1 modulates electrical activity by adjusting PI(4,5)P <sub>2</sub> levels - 于海杰实验室

Significance Cells living in variable environments evolve ways to adapt to altered extracellular conditions. During hypertonic stress, the expression of several human osmolyte transporters increases, thereby accumulating more osmolytes and elevating intracellular osmolarity. We focused on one of these osmolytes, myo-inositol, which is also the precursor of membrane phosphoinositide lipids. We found that intracellular accumulation of myo-inositol via its transporter SMIT1 is able to increase phosphoinositide levels and thereby modulate the activities of phosphoinositide-dependent ion channels. We provide evidence for a previously unidentified connection between the extracellular osmotic changes and the electrical properties of excitable cells. Our findings may help elucidate mechanisms underlying several diseases characterized by either perturbed myo-inositol levels or increased extracellular tonicity.