Issues

Premature stop variants in myosin-binding protein H-like prevent sarcomere incorporation of the translated protein regardless of the location of the premature stop along the protein. Overexpression of truncating variants causes contractile defects in neonatal rat cardiomyocytes.

Combining voltage-clamp fluorometry, kinetic modeling, and molecular dynamics simulation, we show that the auxiliary β-subunit remodels only voltage sensor II and its allosteric contribution to channel opening upon the translocation of two charges before reaching full activation.

Jaque-Fernandez et al. show that depolarization of zebrafish skeletal muscle fibers evokes a Mn²⁺ quenching signal that does not result from store-operated Ca²⁺ entry but from a displacement of Mn²⁺ accumulated on intracellular Ca²⁺ buffers by the increase in intracellular Ca²⁺.

Zhou et al. ask whether distinct β subunit isoforms coassemble in BK channel complexes or segregate into different complexes. Taking advantage of differences in β2- and β3a-mediated inactivation, macroscopic currents, single channels, and biochemical tests unambiguously show that ternary β2:β3:α subunit ternary complexes form, consistent with a trinomial model of random mixing of β subunits.

Ex vivo muscle fiber cultures help scientists study skeletal muscle disease mechanisms, but long-term use causes structural decline and loss-of-function. Vonk, Esen et al. report that 3D culture environments preserve muscle fiber health and contractility better than 2D systems, offering an improved model for drug screening and testing genetic interventions.

Zhou et al. introduce a novel optogenetic approach to control ion channel activity using a photocaged lysine. Combined with VSP, the method provides new insights into PI(4,5)P₂-dependent ion channels and offers a promising tool for in-depth analysis of PI(4,5)P₂-regulated ion transport proteins.