Journal of General Physiology

Adam Feher (The University of Chicago), Zoltan Varga (University of Debrecen) and colleagues examine the molecular mechanism of NZ-58, a novel hHv1 inhibitor. Their findings suggest that it binds to the upper gating triad containing countercharges D112 & D185, leading to a “kinetic trapping” mechanism of inhibition. https://hubs.la/Q04jcvQn0

Varun Verma, Alan S. Verkman and colleagues develop a computational model linking tear production, evaporation, & drainage with ocular surface epithelial transport to predict tear film thickness & osmolality, evaluate current therapies for disease, & propose novel cellular targets. https://hubs.la/Q04hFdny0

Yenisleidy Lorenzo-Ceballos, Christopher J. Lingle et al. (WashU Medicine) show that long-term inactivation (LTI) of Naᵥ1.2 channels mediated by A-isoforms of different FGF homologues (FGF11–FGF14) differ both in intrinsic rates of onset and rates of recovery from LTI. https://hubs.la/Q04hFtsJ0

Using specific gene subunit knockout mice, Rosa Scala, Yuezhou Chen et al. of the Colin Nichols lab show that KATP channels formed exclusively of SUR2/Kir6.2 cause delayed fatigue and development of unstimulated force in isolated EDL skeletal muscles. This suggests similar contractile deficits will be present in ABCC9-dependent intellectual disability myopathy syndrome and KCNJ11-dependent neonatal diabetes. https://hubs.la/Q04hl3Qc0

Magalí Colomer-Molera, Daniel Sastre, and Antonio Felipe (Universitat de Barcelona) reveal that a KCNE4 polymorphism differentially regulates Kv1.3 activity. This work highlights how the size and charge of a single residue within an anionic cluster critically shape the function of Kv1.3. https://hubs.la/Q04hldsw0

Valeriy Lukyanenko, Joaquin Muriel, Noah Weisleder, Robert J. Bloch (University of Maryland School of Medicine) et al. show that dysferlin’s N-terminal C2 domain, DysfC2A, regulates Ca2⁺ signaling and membrane repair specifically. https://hubs.la/Q04gD61q0

Jörg Striessnig (University of Innsbruck) highlights recent work by Hussey et al. (https://hubs.la/Q04gsvLJ0) showing dysregulation of neuronal Caᵥ1.3 and Caᵥ2.1 Ca2⁺ channels as a potential pathogenic mechanism contributing to neurological symptoms associated with calmodulinopathies. https://hubs.la/Q04gskxv0

New review: Yichen Liu, Ramón Latorre, Francisco Bezanilla et al. discuss the main advances in our understanding of fast sodium channel inactivation since the original work of Hodgkin and Huxley to the present era of structural biology. https://hubs.la/Q04fQ7W-0

Our May issue is here! https://hubs.la/Q04fly8s0
The cover represents beat-locked mitochondrial ATP consumption in a sinoatrial node pacemaker myocyte. From Muñoz, Santana and colleagues: https://hubs.la/Q04flj5m0

Using a combination of biophysical and computational approaches, Amin Akhshi, Maurice J. Chacron, Anmar Khadra et al. (McGill University) determine how morphological, intrinsic, and extrinsic factors shape spiking activity in vivo. The computational model was fitted to spiking experimental data, and the variations in the resulting parameters were used to predict the altered spiking activity. Our methodology is likely applicable to other systems and species. https://hubs.la/Q04dVg5z0