2000
DOI: 10.1152/ajpcell.2000.278.2.c277
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Charged residues in the M2 region of α-hENaC play a role in channel conductance

Abstract: The epithelial Na(+) channel (ENaC) is a low-conductance channel that is highly selective for Na(+) and Li(+) over K(+) and impermeable to anions. The molecular basis underlying these conduction properties is not well known. Previous studies with the ENaC subunits demonstrated that the M2 region of alpha-ENaC is critical to channel function. Here we examine the effects of reversing the negative charges of highly conserved amino acids in alpha-subunit human ENaC (alpha-hENaC) M1 and M2 domains. Whole cell and s… Show more

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Cited by 26 publications
(27 citation statements)
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“…2A). Interestingly, all mutants with cysteine substitutions of negatively charged residues displayed smaller currents than wild type, consistent with the observations of Langloh et al (9). Because levels of Na ϩ current expression vary between different batches of oocytes, we compared current expression of wild type and mutant mENaCs in a paired manner.…”
Section: Mutations Within Menac M2 Domains Results In Reducedsupporting
confidence: 85%
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“…2A). Interestingly, all mutants with cysteine substitutions of negatively charged residues displayed smaller currents than wild type, consistent with the observations of Langloh et al (9). Because levels of Na ϩ current expression vary between different batches of oocytes, we compared current expression of wild type and mutant mENaCs in a paired manner.…”
Section: Mutations Within Menac M2 Domains Results In Reducedsupporting
confidence: 85%
“…Our results indicate that point mutations at any of the three negatively charged residues in the M2 domain of ␣mENaC subunit significantly reduced amiloride-sensitive Na ϩ currents, and expression of channels with either double (␣␤D544C ␥D562C) or triple (␣D602C ␤D544C ␥D562C) mutations of the negatively charged residues with ENaC M2 domains failed to produce measurable amiloride-sensitive Na ϩ current in agreement with observations of Langloh et al (9). The reduction in whole cell Na ϩ currents observed with point mutations of polar residues within mENaC M2 domains, as well as the reduction in single-channel Li ϩ conductance previously reported with ␣D575R␤␥ hENaC (human ␣Asp 575 and mouse ␣Asp 602 are at equivalent positions within ␣ENaC), are consistent with the notion that these acidic residues may line the conduction pore and their side chains may provide ion-binding sites (9). Alternatively, these charged residues may have a role in maintaining proper channel conformation, and mutations within M2 domains may disrupt or destabilize the conformation of the channel pore, leading to a reduction of ion conduction.…”
Section: Fig 5 Representative Two-electrode Voltage Clamp Recordingsupporting
confidence: 92%
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