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Cover Image
Cover Image
ON THE COVER
Uptake of fluorescent dextrans in the brain following intracisternal infusion in low versus high volumes. Low-volume infusion of three different-sized dextrans produces minimal uptake in the cortical perivascular spaces (top), whereas high-volume infusion produces extensive perivascular uptake (bottom). Image © Smith et al., 2021. See http://doi.org/10.1085/jgp.202112898. - PDF Icon PDF LinkTable of Contents
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Research News
A TREK inhibitor takes multiple tracks
Single-channel recordings reveal that norfluoxetine inhibits the two-pore domain K+ channel TREK-2 by a complex array of mechanisms.
Commentary
Unraveling the mysteries of the titin–N2A signalosome
The sarcomeric titin springs and accessory proteins modulate muscle force and mechanical signaling at the N2A signalosome.
Articles
Norfluoxetine inhibits TREK-2 K2P channels by multiple mechanisms including state-independent effects on the selectivity filter gate
Proks et al. show that the antidepressant norfluoxetine affects the behavior of TREK-2 two-pore domain K+ channels by regulating the equilibrium between their open and closed states as well as their filter gating.
Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake
Smith et al. use a novel technique for direct measurement of solute transport from cerebrospinal fluid to brain interstitial fluid. Contrary to previous suggestions, they find no evidence for a role of aquaporin-4 in this process of extracellular transport in the central nervous system.
Cooperative binding ensures the obligatory melibiose/Na+ cotransport in MelB
Hariharan and Guan find that binding of either melibiose or Na+ to their transporter, MelB, may favor MelB open states, while cooperative binding may trigger dehydration and cavity closure, thus enforcing cotransport. Cooperative binding is the core mechanism for their cotransport.
ENaC and ROMK channels in the connecting tubule regulate renal K+ secretion
Yang et al. study changes in the activity of the kidney ENaC and ROMK channels in response to variations in K+ levels in the diet. Na+ channel activity and localization changed in response to varying K+ levels, suggesting adaptation in the nephron to compensate for excess or lack of K+.
Intercalated disk nanoscale structure regulates cardiac conduction
Moise et al. develop a finite element model of the intercalated disk (ID) that takes into account the nanoscale structure. Incorporating these details in a cardiac tissue model predicts that alterations in ID structure can affect electrical conduction in the heart.
Zinc binding alters the conformational dynamics and drives the transport cycle of the cation diffusion facilitator YiiP
Lopez-Redondo et al. use cryo-EM and molecular dynamics to evaluate the effects of Zn2+ binding on the conformation and dynamics of the zinc/proton antiporter YiiP. Removal of Zn2+ leads to enhanced conformational dynamics and causes a transition to an intermediate state in the transport cycle.
Cardiac mechanical efficiency is preserved in primary cardiac hypertrophy despite impaired mechanical function
Han et al. study the effect of primary cardiac hypertrophy on cardiac mechano-energetics. Using isolated cardiac tissues, they show that despite impaired contractile performance, cardiac mechanical efficiency is preserved in hypertrophic hearts.
Communications
Mutation of a conserved glutamine residue does not abolish desensitization of acid-sensing ion channel 1
Rook et al. assess how mutations in acid-sensing ion channel 1 (ASIC1) affect channel desensitization. They establish that, contrary to previous reports, a glutamine to glycine substitution does not abolish desensitization, but causes complex pH-dependent effects on channel desensitization.
