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Shen et al. show that mutating countercharge residues in Ciona intestinalis voltage-sensing phosphatase result in the formation of a continuous water path through the voltage-sensing domain and the generation of omega currents. Their work reveals a novel role for voltage-sensor countercharges.

Enamel-forming cells direct the transport of calcium out of the cell to help mineralize the enamel crystals. Sodium/calcium exchangers are proteins that efficiently extrude calcium. In enamel cells, NCKX proteins dominate this function explaining why patients with defective NCKX4 have enamel defects.

VPC01091.4 and AAL-149 are FTY720 analogs that inhibit TRPM7 without targeting S1P receptors and exert multimodal anti-inflammatory effects in vivo. In a mouse endotoxemia model, VPC01091.4 reduces inflammation and disease severity without impacting blood lymphocyte counts.

TRPV1 ion channels are important players in thermal and chemical sensation and have roles in pathological states. In this work, Garcia-Ávila et al. employ single-channel recordings to observe that large cations are more permeable than smaller ones and uncover fast conformational changes that are distinctly modulated by the cation occupying the pore.

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