ArticleAmerican journal of physiology. Cell physiology2013
Regulation of large-conductance Ca2+-activated K+ channels by WNK4 kinase.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- The exquisite link between potassium homeostasis regulation and cardiovascular health: exploration and analysis.Frontiers in physiology · 2026Review
- The endocytic adaptor ARH facilitates potassium conservation by regulating ROMK and BK.American journal of physiology. Renal physiology · 2025Article
- Paraoxonase 3 regulates the pore-forming α subunit of the large-conductance KBiochimica et biophysica acta. Molecular cell research · 2025Article
- Circadian Rhythm Regulation by Pacemaker Neuron Chloride Oscillation in Flies.Physiology (Bethesda, Md.) · 2024Review
- Potassium Homeostasis and WNK Kinases in the Regulation of the Sodium-Chloride Cotransporter: Hyperaldosteronism and Its Metabolic Consequences.Kidney360 · 2022Article
- Chloride oscillation in pacemaker neurons regulates circadian rhythms through a chloride-sensing WNK kinase signaling cascade.Current biology : CB · 2022Article
- BK Channel Deficiency in Osteoblasts Reduces Bone Formation via the Wnt/β-Catenin Pathway.Molecules and cells · 2021Article
- L-WNK1 is required for BK channel activation in intercalated cells.American journal of physiology. Renal physiology · 2021Article
- WNK4 kinase: from structure to physiology.American journal of physiology. Renal physiology · 2021Review
- Crosstalk between phosphorylation and ubiquitination is involved in high salt-induced WNK4 expression.Experimental and therapeutic medicine · 2021Article
- Coronary Large Conductance CaFrontiers in physiology · 2021Review
- 14-3-3γ, a novel regulator of the large-conductance CaAmerican journal of physiology. Renal physiology · 2020Article
- Stimulatory Role of SPAK Signaling in the Regulation of Large Conductance CaFrontiers in physiology · 2020Article
- BK Channel Dysfunction in Diabetic Coronary Artery: Role of the E3 Ubiquitin Ligases.Frontiers in physiology · 2020Review
- Intercalated Cells of the Kidney Collecting Duct in Kidney Physiology.Seminars in nephrology · 2019Review
- The renal TRPV4 channel is essential for adaptation to increased dietary potassium.Kidney international · 2017Article
- Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels.Frontiers in physiology · 2017Review
- ROMK expression remains unaltered in a mouse model of familial hyperkalemic hypertension caused by the CUL3Δ403-459 mutation.Physiological reports · 2016Article
- The CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy.American journal of physiology. Renal physiology · 2016Article
- An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron.American journal of physiology. Cell physiology · 2016Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Large-conductance, Ca(2+)-activated K(+) channels, commonly referred to as BK channels, have a major role in flow-induced K(+) secretion in the distal nephron. With-no-lysine kinase 4 (WNK4) is a serine-threonine kinase expressed in the distal nephron that inhibits ROMK activity and renal K(+) secretion. WNK4 mutations have been described in individuals with familial hyperkalemic hypertension (FHHt), a Mendelian disorder characterized by low-renin hypertension and hyperkalemia. As BK channels also have an important role in renal K(+) secretion, we examined whether they are regulated by WNK4 in a manner similar to ROMK. BK channel activity was inhibited in a rabbit intercalated cell line transfected with WNK4 or a WNK4 mutant found in individuals with FHHt. Coexpression of an epitope-tagged BK α-subunit with WNK4 or the WNK4 mutant in HEK293 cells reduced BK α-subunit plasma membrane and whole cell expression. A region within WNK4 encompassing the autoinhibitory domain and a coiled coil domain was required for WNK4 to inhibit BK α-subunit expression. The relative fraction of BK α-subunit that was ubiquitinated was significantly increased in cells expressing WNK4, compared with controls. Our results suggest that WNK4 inhibits BK channel activity, in part, by increasing channel degradation through an ubiquitin-dependent pathway. Based on these results, we propose that WNK4 provides a cellular mechanism for the coordinated regulation of two key secretory K(+) channels in the distal nephron, ROMK and BK.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.