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Cover Image
Cover Image
ON THE COVER
The capillaries (green) of cardiac ventricles weave through the tightly packed myocytes (blue) and are intimately adorned with pericytes (red) along their lengths. These pericytes also send processes ("microtubes") which bridge the gap to other nearby capillary segments by extending intimately through and around myocytes. In this issue, Longden and Lederer hypothesize that the cellular and molecular organization of at least these three cell types plays a crucial role in orchestrating blood flow regulation in the microcirculation of the heart, brain, and other organs via the process of electro-metabolic signaling. Image courtesy of Guiling Zhao, University of Maryland School of Medicine, Baltimore, MD, USA. See https://doi.org/10.1085/jgp.202313451. - PDF Icon PDF LinkTable of Contents
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Editorial
Research News
How PKA helps cardiomyocytes Navigate chronic stress
JGP study suggests that, by altering microtubule dynamics, persistent PKA activation promotes the delivery of Nav1.5 channels to intercalated discs.
Articles
Persistent PKA activation redistributes NaV1.5 to the cell surface of adult rat ventricular myocytes
Bernas et al. show that persistent PKA activation increases INa by directing NaV1.5 to the myocyte surface, activating CREB1, upregulating EB1, and reorganizing microtubules. Their study suggests that persistent PKA activation may protect impulse propagation in a chronically stressed heart.
Elucidating molecular mechanisms of protoxin-II state-specific binding to the human NaV1.7 channel
NaV1.7, a voltage-gated sodium channel, plays a crucial role in pain perception and is specifically targeted by PTx2, which serves as a template for designing pain therapeutics. In this study, Ngo et al. employed computational modeling to evaluate the state-dependent binding of PTx2 to NaV1.7.
Mechanism of hydrophobic gating in the acetylcholine receptor channel pore
Nicotinic acetylcholine receptors (AChRs) play critical roles in muscle contraction and cognition. Kumari et al. elucidate the mechanism of AChR gate opening and show why mutations at the gate result in constitutive channel openings that cause congenital disorders.
Asymmetric contribution of a selectivity filter gate in triggering inactivation of CaV1.3 channels
Inactivation of calcium channels is an important feedback mechanism that limits excessive calcium influx into cells. This study identifies asymmetric conformational changes in the selectivity filter as critical for orchestrating channel inactivation. Destabilizing the selectivity filter could reverse deficits in inactivation linked to Timothy syndrome.
Hypothesis
Electro-metabolic signaling
Longden and Lederer propose a detailed electro-metabolic signaling hypothesis, describing a set of mechanisms that may operate in a diverse array of systems to precisely match local energy demand with supply via capillary electrical signaling to control blood flow.
