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Cover Image
Cover Image
ON THE COVER
Yeast-two hybrid assay images showing the growth of yeast-cells expressing AnkB and SUR2A WT (blue, left) or p.S1054Y (orange, right). Superimposed unitary currents (white) generated by cells expressing Kir6.2 and SUR2A WT (left) or p.S1054Y (right). The inset (top right) shows an expanded view of the multiple conductance states induced by p.S1054Y SUR2A. Image © Crespo-García et al., 2022. See https://doi.org/10.1085/jgp.202112995. - PDF Icon PDF LinkTable of Contents
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Commentary
Variants of the myosin interacting-heads motif
The two heads of myosin II interact with each other and with the proximal part of the myosin tail, forming the interacting-heads motif (IHM). The IHM is normally thought of as a single, unique structure, but there are several variants, with important energetic and pathophysiological consequences.
Calcium activation through thick and thin?
A historical perspective of the super-relaxed (SRX) state, interacting heads motif (IHM), and impact of calcium on muscle contractility.
Reviews
Mechanistic insights on KATP channel regulation from cryo-EM structures
Driggers and Shyng present a comprehensive review of recent advances in cryo-EM structures of KATP channels and the insights from these structures on the mechanisms of channel gating and pharmacology.
Articles
Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils
Control of muscle contraction is still not understood. Here, we image fluorescently tagged ATP with single-molecule precision to reveal the activity of individual myosins in different sarcomeric locations. We show how treatment with PKA and the FDA-approved drug mavacamten affects relaxed myofibrils.
Huntingtin regulates calcium fluxes in skeletal muscle
The Huntingtin protein, well known for its involvement in the neurodegenerative Huntington’s disease, is also expressed in skeletal muscle. The work presented here is dedicated to a better understanding of its function in skeletal muscle through the development and characterization of KO models.
A Cantú syndrome mutation produces dual effects on KATP channels by disrupting ankyrin B regulation
The Cantú syndrome–associated p.S1054Y SUR2A mutation increases open probability and conductance of ATP-sensitive (KATP) channels by inducing the appearance of multiple conductance states and reduces the membrane expression of channel subunits. These alterations were corrected by overexpression of ankyrin B. Thus, this mutation impairs the physiological interaction between ankyrin B and KATP channels.
cAMP-PKA signaling modulates the automaticity of human iPSC-derived cardiomyocytes
The automaticity of human-induced pluripotent stem cell–derived cardiomyocytes is regulated by a coupled-clock system of the Ca2+ and membrane clocks. We found that the coupled-clock system is regulated by local Ca2+ releases and cAMP/PKA-dependent coupling of the Ca2+ clock to the membrane clock.
Communications
KCa1.1 channels contribute to optogenetically driven post-stimulation silencing in cerebellar molecular layer interneurons
Optical activation of channel rhodopsin is used to increase neuronal activity. In cerebellar interneurons, it actually leads to a biphasic activation/inhibition sequence. In these cells, activation of KCa1.1 channels contributes to the post-stimulus inhibition.
