title: βENaC is required for whole cell mechanically gated currents in renal vascular smooth muscle cells.
abstract: Myogenic constrictor responses in small renal arteries and afferent arterioles are suppressed in mice with reduced levels of β-epithelial Na⁺ channel (βENaC(m/m)). The underlying mechanism is unclear. Decreased activity of voltage-gated calcium channels (VGCC) or mechanically gated ion channels and increased activity of large conductance calcium-activated potassium (BK) channels are a few possible mechanisms. The purpose of this study was to determine if VGCC, BK, or mechanically gated ion channel activity was altered in renal vascular smooth muscle cell (VSMC) from βENaC(m/m) mice. To address this, we used whole cell patch-clamp electrophysiological approaches in freshly isolated renal VSMCs. Compared with βENaC(+/+) controls, the current-voltage relationships for VGCC and BK activity are similar in βENaC(m/m) mice. These findings suggest neither VGCC nor BK channel dysfunction accounts for reduced myogenic constriction in βENaC(m/m) mice. We then examined mechanically gated currents using a novel in vitro assay where VSMCs are mechanically activated by stretching an underlying elastomer. We found the mechanically gated currents, predominantly carried by Na⁺, are observed with less frequency (87 vs. 43%) and have smaller magnitude (-54.1 ± 12.5 vs. -20.9 ± 4.9 pA) in renal VSMCs from βENaC(m/m) mice. Residual currents are expected in this model since VSMC βENaC expression is reduced by 50%. These findings suggest βENaC is required for normal mechanically gated currents in renal VSMCs and their disruption may account for the reduced myogenic constriction in the βENaC(m/m) model. Our findings are consistent with the role of βENaC as a VSMC mechanosensor and function of evolutionarily related nematode degenerin proteins.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Wen-Shuo
authors.initials: WS
authors.lastname: Chung
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Weissman
authors.forename: Jerry
authors.initials: J
authors.lastname: Farley
authors.forename: Heather A
authors.initials: HA
authors.lastname: Drummond
mesh_terms: D000818:Animals; D053503:Epithelial Sodium Channels / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000502:physiology; D008465:Mechanoreceptors / Q000502:physiology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: D053503:Epithelial Sodium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C507049:Scnn1b protein, mouse
keywords: degenerin; epithelial Na+ channel; ion channel; myogenic constriction
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