Intercalated cell BKα subunit is required for flow-induced K+ secretion

Carrisoza-Gaytán, Rolando; Ray, Evan C.; Flores, Daniel; Marciszyn, Allison L.; Wu, Peng; Liu, Leah; Subramanya, Arohan R.; Wang, Wenhui; Sheng, Shaohu; Nkashama, Lubika J.; Chen, Jingxin; Jackson, Edwin K.; Mutchler, Stephanie; Heja, Szilvia; Kohan, Donald E.; Satlin, Lisa M.; Kleyman, Thomas R.

doi:10.1172/jci.insight.130553

Cited by 36 publications

(40 citation statements)

References 68 publications

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“…Previous work has suggested that L-WNK1 activates BK channels by inhibiting ERK1/2-dependent channel degradation (28). BK channels are responsible for FIKS (6,7,33,46,52). While BK channels are expressed in both PCs and ICs, our recent work suggests that BK channels in ICs mediate FIKS (7).…”

Section: Discussionmentioning

confidence: 78%

“…Patch-clamp electrophysiology: BK channel activity was assessed via perforated whole-cell recording of ICs in micro-dissected, split open CCDs from IC-L-WNK1-KO and littermate control mice on a high K + diet for 10 days, as previously described (7). The bath solution contained (in mM) 130 K + gluconate, 10 KCl, 0.5 MgCl2, 1.5 CaCl2, 10 HEPES, pH 7.4, whereas the pipette solution had 130 K + gluconate, 10 KCl, 1 MgCl2, 8.72 CaCl2, 10 EGTA (1 μM free Ca 2+ ), 5 HEPES, pH 7.4.…”

Section: Generation Of Ic-specific L-wnk1-ko Micementioning

confidence: 99%

“…An iberiotoxin-sensitive, large conductance, Ca 2+ -and/or stretch-activated K + channel, referred to as BK or K Ca 1.1, has a critical role in flow-induced K + secretion (FIKS) in the ASDN (6, 7, 33, 46, 52). A high K + environment (in salamanders) or high K + diet (in rabbits and mice) stimulated apical expression of this channel as well as BK channel-mediated K + secretion in the collecting duct (CD) (2, 7, 9, 33, 46, 52). A global knock-out of the mouse BK α or β1 subunit provided support for the role of BK channels in renal K + secretion (39, 40).…”

mentioning

confidence: 99%

“…ENaC dependent Na + absorption in the ASDN has an important role in K + secretion and FIKS (25, 35), although ENaC independent K + secretion has been observed (14). BK channels are expressed in both principal cells (PCs) and ICs (7, 9, 13, 33, 36). The question of whether BK channels in PCs, ICs or both cell types are responsible for FIKS has been addressed by several groups.…”

mentioning

confidence: 99%

“…Transition of rabbits to a high K + diet increases BKα subunit expression primarily in ICs, rather than PCs (9). In mice, an IC-selective knockout of the BKα subunit abolished FIKS in isolated, perfused CCDs from these animals and was associated with an increased blood [K + ], at least in male mice on a high K + diet (7).…”

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confidence: 99%

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L-WNK1 is required for BK channel activation in intercalated cells

Ray

Carrisoza-Gaytán

Al‐bataineh

et al. 2021

Preprint

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BK channels expressed in intercalated cells (ICs) in the aldosterone-sensitive distal nephron (ASDN) mediate flow-induced K+ secretion. In the ASDN of mice and rabbits, IC BK channel expression and activity increase with a high K+ diet. In cell culture, the long isoform of the kinase WNK1 (L-WNK1) increases BK channel expression and activity. Apical L-WNK1 expression is selectively enhanced in ICs in the ASDN of rabbits on a high K+ diet, suggesting that L-WNK1 contributes to BK channel regulation by dietary K+. We examined the role of IC L-WNK1 expression in enhancing BK channel activity in response to a high K+ diet. Mice with an IC-selective deletion of L-WNK1 (IC-L-WNK1-KO) and littermate control mice were placed on a high K+ (5% K+ as KCl) diet for at least 10 days. IC-L-WNK1-KO mice exhibited higher blood K+ concentrations ([K+]) than controls. BK channel-dependent whole-cell currents in ICs from cortical collecting ducts of high K+ fed IC-L-WNK1-KO mice were reduced compared to controls. Six-hour urinary K+ excretion in response a saline load was similar in IC-L-WNK1-KO mice and controls. The observations that IC-L-WNK1-KO mice have higher blood [K+] and reduced IC BK channel currents are consistent with impaired urinary K+ secretion, and suggest that IC L-WNK1 has a role in the renal adaptation to a high K+ diet.

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Section: Discussionmentioning

confidence: 78%

Section: Generation Of Ic-specific L-wnk1-ko Micementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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L-WNK1 is required for BK channel activation in intercalated cells

Ray

Carrisoza-Gaytán

Al‐bataineh

et al. 2021

Preprint

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Aldosterone: Renal Action and Physiological Effects

Johnston

Welch

Cain

et al. 2023

Comprehensive Physiology

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Epithelial Na ⁺ Channels Function as Extracellular Sensors

Kashlan,

Wang,

Sheng

et al. 2024

Comprehensive Physiology

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The epithelial Na + channel (ENaC) resides on the apical surfaces of specific epithelia in vertebrates and plays a critical role in extracellular fluid homeostasis. Evidence that ENaC senses the external environment emerged well before the molecular identity of the channel was reported three decades ago. This article discusses progress toward elucidating the mechanisms through which specific external factors regulate ENaC function, highlighting insights gained from structural studies of ENaC and related family members. It also reviews our understanding of the role of ENaC regulation by the extracellular environment in physiology and disease. After familiarizing the reader with the channel's physiological roles and structure, we describe the central role protein allostery plays in ENaC's sensitivity to the external environment. We then discuss each of the extracellular factors that directly regulate the channel: proteases, cations and anions, shear stress, and other regulators specific to particular extracellular compartments. For each regulator, we discuss the initial observations that led to discovery, studies investigating molecular mechanism, and the physiological and pathophysiological implications of regulation. © 2024 American Physiological Society. Compr Physiol 14:5407‐5447, 2024.

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Intercalated cell BKα subunit is required for flow-induced K+ secretion

Cited by 36 publications

References 68 publications

L-WNK1 is required for BK channel activation in intercalated cells

L-WNK1 is required for BK channel activation in intercalated cells

Aldosterone: Renal Action and Physiological Effects

Epithelial Na ⁺ Channels Function as Extracellular Sensors

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Intercalated cell BKα subunit is required for flow-induced K+ secretion

Cited by 36 publications

References 68 publications

L-WNK1 is required for BK channel activation in intercalated cells

L-WNK1 is required for BK channel activation in intercalated cells

Aldosterone: Renal Action and Physiological Effects

Epithelial Na + Channels Function as Extracellular Sensors

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Product

Resources

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Epithelial Na ⁺ Channels Function as Extracellular Sensors