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Fusion of mononucleated primary murine muscle progenitor cells produces multinucleated muscle fibers in vitro. A representative image of multinucleated muscle fibers produced in vivo by the differentiation of mononucleated muscle precursor cells isolated from murine hindlimbs. Mononucleated muscle progenitor cells were differentiated for 36 h in culture by switching to low serum media. This stimulus promoted the myogenic differentiation of this mononucleated cell population. The cells then fused to produce large myofibers containing tens to hundreds of nuclei. The fibers are stained for the actin cytoskeleton (red, phalloidin) and myonuclei (blue, DAPI) to demonstrate the fiber architecture and the nuclei within them. See page 1498.
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Sexual harassment has plagued academic science with too little progress over the last decades. A new report from the National Academies of Science, Engineering, and Medicine provides data and guidance for making real advances.
Bezanilla recalls the profound influence that the Laboratory of Cell Physiology in Montemar, with its investigators and visitors, have had in shaping his scientific career.
Milestone in Physiology
JGP 100th Anniversary
BEST1 is a chloride channel that is activated by calcium. Vaisey and Long demonstrate that ionic currents through BEST1 inactivate by an allosteric mechanism in which the binding of a C-terminal peptide to a surface-exposed receptor controls a physically distant inactivation gate within the pore.
Limb-girdle muscular dystrophy type 2L arises from mutations in the anoctamin ANO5, whose role in muscle physiology is unknown. Whitlock et al. show that loss of ANO5 perturbs phosphatidylserine exposure and cell–cell fusion in muscle precursor cells, which is an essential step in muscle repair.
Nebulin increases thin filament stiffness and force per cross-bridge in slow-twitch soleus muscle fibers
Nebulin stabilizes the thin filament and regulates force generation in skeletal muscle, but its precise role is not understood. Using conditional knockout mice, Kawai et al. demonstrate that nebulin functions to increase the force per cross-bridge in skinned slow-twitch soleus muscle fibers.
Kinetic properties of persistent Na+ current orchestrate oscillatory bursting in respiratory neurons
Intrinsically oscillatory neurons in the pre-Bötzinger complex contribute to the rhythmic pattern of breathing. Yamanishi et al. show that the slow inactivation and slow recovery from inactivation exhibited by the persistent sodium current are important for bursting activity in these neurons.
Inwardly rectifying potassium (Kir) channels experience strong (blocking) and weak (intrinsic) rectification. Linkage analysis in the form of a conductance Hill plot is a sensitive method of resolving allosteric interactions between the pore and mediators of the Kir gating process.
TRPV1 channels comprise four subunits containing six transmembrane segments (S1–S6) that surround a central pore. Kasimova et al. hypothesize that channel opening involves rotation of an S6 asparagine residue toward the pore, as well as associated pore hydration and external cavity dehydration.
Methods and Approaches
FRET-based biosensors are powerful tools to study intracellular signaling that require long culture times for adenoviral infection. Reddy et al. have developed a method for culturing adult mouse cardiomyocytes involving blebbistatin, which preserves cell morphology for up to 50 h after adenoviral infection.
Voltage-gated Na+ and K+ channels are known to underlie the temporal characteristics of action potentials. Corbin-Leftwich et al. establish reliable action potential recordings from Xenopus oocytes coexpressing these channels and show how different K+ channel subtypes can modulate excitability.