Not so transport incompetent after all: Revisiting a CLC-7 mutant sheds new mechanistic light on lysosomal physiology
Accardi reviews data on the lysosomal 2 Cl−/1 H+ antiporter ClC-7.
A new structure of a CLC antiporter mutant, along with EPR spectroscopy and computational dynamics, now resolves several basic puzzles regarding how these transporters stoichiometrically move Cl− and H+ in opposite directions across biological membranes.
Obashi et al. review the regulation of molecular diffusion by dendritic spine structures and discuss its role in synaptic functions and plasticity.
Detection of Ca2+ transients near ryanodine receptors by targeting fluorescent Ca2+ sensors to the triad
Sanchez et al. target the Ca2+-sensitive dye CGaMP6f to the triad region of the sarcomere by using the T306 domain of triadin. Their approach reveals synchronous Ca2+ release across individual triads and will facilitate the study of ryanodine receptor channel function.
Fast inactivation of Nav current in rat adrenal chromaffin cells involves two independent inactivation pathways
Martinez-Espinosa et al. show that fast and slow recovery of voltage-dependent Na+ (Nav) channels in rat adrenal chromaffin cells depends on two independent inactivation pathways. Competition between these pathways regulates changes in Nav channel availability.
Nav1.3 and FGF14 are primary determinants of the TTX-sensitive sodium current in mouse adrenal chromaffin cells
Martinez-Espinosa et al. show that FGF14 and the voltage-dependent Na+ channel Nav1.3 are the main regulators of rapidly inactivating currents and Nav channel availability in mouse adrenal chromaffin cells. Their results uncover a role for FGF14 in regulating Nav channel function.
A mouse model of Huntington’s disease shows altered ultrastructure of transverse tubules in skeletal muscle fibers
This study reveals defects in the transverse tubules of skeletal muscle in the R6/2 model of Huntington’s disease. These results serve as a foundation to simulate electrical activity in skeletal muscle and may help explain the motor deficits in Huntington’s disease patients.
Resin-acid derivatives bind to multiple sites on the voltage-sensor domain of the Shaker potassium channel
Silverå Ejneby et al. use molecular dynamics simulations and electrophysiology to show that the voltage-gated Shaker potassium channel has multiple binding sites for resin-acid derivatives that can regulate its opening.
In silico simulations reveal that RYR distribution affects the dynamics of calcium release in cardiac myocytes
Iaparov et al. use in silico modeling to test the effect of changes in the geometric arrangement of RYR channels on calcium release in cardiac myocytes. Their simulations predict a coupling between RYR distribution at the calcium release site and dyad function.
DEG/ENaC/ASIC channels vary in their sensitivity to anti-hypertensive and non-steroidal anti-inflammatory drugs
Animal physiology depends on degenerin, epithelial sodium, and acid-sensing ion channels (DEG/ENaC/ASICs). By measuring the sensitivity of three C. elegans DEG/ENaC/ASICs to amiloride analogs and NSAIDs, Fechner et al. show that individual channels have distinct pharmacological footprints.