Issues

During the fast block to polyspermy, fertilization activates a phospholipase C (PLC) to signal a depolarization in Xenopus laevis eggs. Komondor and colleagues investigated how fertilization activates PLC and ruled out the conventional signaling pathways including tyrosine phosphorylation of PLCγ1 or G-protein activation of PLC β1/3.

Urea transport by UT-B in human RBC shows a >10-fold donor variation in contrast to the transport of anions, glucose, and water. The study supports the proposal that urea and water share no pathway in common. The donor-to-donor variation must be considered in urea transport studies.

Both myofilaments and mitochondria restrict longitudinal diffusion in murine cardiac myocytes. Porin channels in the outer mitochondrial membrane allow long-distance diffusion to occur through intramembrane mitochondrial spaces. Diffusion restrictions may be important determinants of AMP and ADP signaling.

KCNQ1-activating polyunsaturated fatty acid (PUFA) analogs bind preferentially to different sites on KCNQ1. PUFA analog binding between S3 and S4 leads to the strongest shift in voltage dependence. These insights can help to aid drug development for long QT syndrome.

Krumbach et al. use molecular dynamics simulations to study the open HCN4 pore with different monovalent cations. Their simulations recapitulate experimental findings on cation-specific permeation and blocking of the channel and stress a mutual adaptation of cations and filter geometry as the basis for cation selectivity.

Hundreds of genetic variants in the voltage-gated sodium channel Na_V1.2 are associated with a spectrum of neurodevelopmental disorders with or without epilepsy. High throughput automated patch-clamp recording of several variants revealed more complex patterns of dysfunction than previously recognized.

It is surprising that osmosis, a phenomenon so central to biology, has been cloaked in misunderstanding for so long. The authors show that the most plausible account for what drives water fluxes is one put forward by Peter Debye in 1923, where the repulsion of solute molecules from the semipermeable membrane generates a pressure drop, which draws water from a chamber with low solute concentration to one that is high.

JGP study reveals that conventional PLC activation pathways are not required for the fertilization-induced depolarization of Xenopus eggs that prevents the entry of additional sperm.