Gain-of-function variant of the human epithelial sodium channel

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Gain-of-function variant of the human epithelial sodium channel.

Epithelial Na(+) channel (ENaC) mutations are associated with several human disorders, underscoring the importance of these channels in human health. Recent human genome sequencing projects have revealed a large number of ENaC gene variations, several of which have been found in individuals with salt-sensitive hypertension, cystic fibrosis, and other disorders. However, the functional consequen...

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Gain-of-Function Mutation W493R in the Epithelial Sodium Channel Allosterically Reconfigures Intersubunit Coupling.

Sodium absorption in epithelial cells is rate-limited by the epithelial sodium channel (ENaC) activity in lung, kidney, and the distal colon. Pathophysiological conditions, such as cystic fibrosis and Liddle syndrome, result from water-electrolyte imbalance partly due to malfunction of ENaC regulation. Because the quaternary structure of ENaC is yet undetermined, the bases of pathologically lin...

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Temperature-dependent model of human cardiac sodium channel

Cardiac sodium channels are integral membrane proteins whose structure is not known at atomic level yet and their molecular kinetics is still being studied through mathematical modeling. This study has focused on adapting an existing model of cardiac Na channel to analyze molecular kinetics of channels at 9-37°C. Irvine et al developed a Markov model for Na channel using Neuronal Network Model ...

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Temperature-dependent model of human cardiac sodium channel

Cardiac sodium channels are integral membrane proteins whose structure is not known at atomic level yet and their molecular kinetics is still being studied through mathematical modeling. This study has focused on adapting an existing model of cardiac Na channel to analyze molecular kinetics of channels at 9-37°C. Irvine et al developed a Markov model for Na channel using Neuronal Network Model ...

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Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel.

We previously reported the existence of multiple isoforms of human Nedd4-2 (Am J Physiol Renal Physiol 285: F916-F929, 2003). When overexpressed in M-1 collecting duct epithelia, full-length Nedd4-2 (Nedd4-2), Nedd4-2 lacking the NH(2)-terminal C2 domain (Nedd4-2DeltaC2), and Nedd4-2 lacking WW domains 2 and 3 (Nedd4-2DeltaWW2,3) variably reduce benzamil-sensitive Na(+) transport. We investigat...

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ژورنال

عنوان ژورنال: American Journal of Physiology-Renal Physiology

سال: 2013

ISSN: 1931-857X,1522-1466

DOI: 10.1152/ajprenal.00563.2012