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Colabeling of Piezo1-GFP and Pannexin1-flag expressed in DAPI-counterstained HEK-P1KO cells. Image © Desplat et al., 2021. See http://doi.org/10.1085/jgp.202112871. - PDF Icon PDF LinkTable of Contents
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Research News
Piezo1 helps bile on the pressure
JGP study shows that a mechanosensitive complex containing Piezo1 and Pannexin1 couples osmotic pressure to ATP secretion in bile duct cholangiocytes.
Commentary
Targeting late ICaL to close the window to ventricular arrhythmias
This commentary is on the paper by Angelini et al. Here, we set the original paper in the context of triggered arrhythmias, particularly early after depolarizations (EADs), emphasizing the importance of pharmacologically inhibiting late Ca2+ current to prevent EADs without affecting myocardial contractility.
Reviews
The molecular evolution of function in the CFTR chloride channel
Features of related ABC proteins provided a unique opportunity for emergence of novel channel function in CFTR by incremental evolution.
Articles
Piezo1–Pannexin1 complex couples force detection to ATP secretion in cholangiocytes
Desplat et al. show that the Piezo1 channel mediates Ca2+ entry into mouse cholangiocytes as a result of mechanical stress due to cell swelling. Piezo1 thus activates and forms complexes with Pannexin1, which result in force-induced ATP release and signal amplification through P2X4R.
Angiotensin 1–7 prevents the excessive force loss resulting from 14- and 28-day denervation in mouse EDL and soleus muscle
Albadrani et al. studied the potential of angiotensin 1–7 to prevent the atrophy that normally ensues muscle denervation. Increasing angiotensin 1–7 levels do not prevent muscle mass loss in denervated muscles but maintain normalized tetanic force to cross-sectional area and membrane excitability for up to 28 d.
Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current
Angelini et al. show that reducing late L-type Ca2+ current with the purine analogue roscovitine is sufficient to suppress ventricular arrhythmias in myocytes and ex vivo hearts. By preserving the early component of ICa,L, this strategy is expected to largely maintain contractility, an advantage over Ca2+ channel blockers.
Pannexin-1 and CaV1.1 show reciprocal interaction during excitation–contraction and excitation–transcription coupling in skeletal muscle
Jaque-Fernández et al. show that downregulation of CaV1.1 in muscle fibers elevates ATP release, whereas downregulation of Panx1 depresses depolarization-induced intracellular Ca2+ release. They conclude that Panx1 is a reciprocal partner of CaV1.1 for both excitation–contraction and excitation–transcription coupling.
ML277 regulates KCNQ1 single-channel amplitudes and kinetics, modified by voltage sensor state
Using single-channel recordings, Eldstrom et al. demonstrate that ML277, a relatively specific activator of KCNQ1 channels, enhances KCNQ1 single-channel kinetics. The data indicate that the pore effects of the drug are at least as important as its well-documented whole-cell gating actions.
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