Potassium: friend or foe?

Rodan, Aylin R.

doi:10.1007/s00467-016-3411-8

Cited by 37 publications

(26 citation statements)

References 117 publications

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“…The results shed light on the pathophysiology of hypertension in potassium deficiency. maintaining K + homeostasis and in the pathogenesis of K + deficiency-induced hypertension (22). Mechanistically, recent in vitro and ex vivo studies lend support for the hypothesis that extracellular K + modulates [Cl − ] i to regulate the activity of NCC via WNKs-SPAK/OSR1 cascade (9,10,23,24).…”

Section: Significancementioning

confidence: 89%

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WNK4 kinase is a physiological intracellular chloride sensor

Chen

Lin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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With-no-lysine (WNK) kinases regulate renal sodium-chloride cotransporter (NCC) to maintain body sodium and potassium homeostasis. Gain-of-function mutations of WNK1 and WNK4 in humans lead to a Mendelian hypertensive and hyperkalemic disease pseudohypoaldosteronism type II (PHAII). X-ray crystal structure and in vitro studies reveal chloride ion (Cl−) binds to a hydrophobic pocket within the kinase domain of WNKs to inhibit its activity. The mechanism is thought to be important for physiological regulation of NCC by extracellular potassium. To test the hypothesis that WNK4 senses the intracellular concentration of Cl−physiologically, we generated knockin mice carrying Cl−-insensitive mutant WNK4. These mice displayed hypertension, hyperkalemia, hyperactive NCC, and other features fully recapitulating human and mouse models of PHAII caused by gain-of-function WNK4. Lowering plasma potassium levels by dietary potassium restriction increased NCC activity in wild-type, but not in knockin, mice. NCC activity in knockin mice can be further enhanced by the administration of norepinephrine, a known activator of NCC. Raising plasma potassium by oral gavage of potassium inactivated NCC within 1 hour in wild-type mice, but had no effect in knockin mice. The results provide compelling support for the notion that WNK4 is a bona fide physiological intracellular Cl−sensor and that Cl−regulation of WNK4 underlies the mechanism of regulation of NCC by extracellular potassium.

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Section: Significancementioning

confidence: 89%

“…NCC-mediated Na + reabsorption in DCT controls Na + delivery to the downstream aldosterone-sensitive distal nephron, where Na + reabsorption via ENaC is important for K + secretion (22). Thus, NCC plays a critical role for K + homeostasis (14,21).…”

Section: Discussionmentioning

confidence: 99%

WNK4 kinase is a physiological intracellular chloride sensor

Chen

Lin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, blood K + was reduced to less than 1.4 mmol/l. This severe hypokalemia is likely the cause of death in SS Kcnj16-/-rats, as it is known to result in respiratory paralysis and/or fatal arrhythmia and sudden cardiac arrest (34).…”

Section: Physiological Consequences Of a Kcnj16 Knockout Upon Salt-inmentioning

confidence: 99%

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

Palygin¹,

Levchenko²,

Ilatovskaya³

et al. 2017

JCI Insight

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“…Therefore, cortisol can stimulate renal transport processes conventionally attributed to the reninangiotensin-aldosterone-system (RAAS), and its high concentration during exercise, could help maintain the stability of Na + ion in the blood serum. The K + ion is the most abundant intracellular cation, and its concentration in the extracellular space is low due to the action of the Na + /K + -ATPase which pumps three Na + ion out of the cell in exchange for two K + ion (Rodan, 2016). Thus, 98% of total body K + ion is found in intracellular stores, chiefly in muscle (Terker et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Effects of exercise on cations/anions in blood serum of English Thoroughbred horses

Prado-Rebolledo

Morales

García

et al. 2019

Arq. Bras. Med. Vet. Zootec.

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English Thoroughbred horses, are widespread in Mexico and due to the lack of data on their exercise physiology, it is important to conduct exercise tests in order to obtain information the effects of exercise on more essential cations/anions in blood serum, as these horses are submitted to constant efforts. The study was carried out with 150 blood samples of English Thoroughbred horses clinically healthy. The blood sample collection was performed during three periods: 1) rest, 2) 30min after exercise (speed race of 12km/h for 30min with no rest) and 3) 60min after exercise. Mean values were calculated for cations (sodium and potassium) and anions (chloride and bicarbonate). The resulting data set was analyzed using Gaussian distribution and descriptive statistics. Confidence intervals of 95% were established. The linear relationships between ions were quantified, and an analysis of variance was performed to compare the mean values between groups. The concentrations of the described analytes are consistent with values reported by international literature. The comparison between groups, revealed that during exercise, sodium ion did not show changes 30min after exercise and increase 60min after. Potassium ion showed increase 30min after exercise and decrease 60min after. Chloride ion showed a decrease 30min after exercise, to recover gradually 60min after. Meanwhile, bicarbonate ion showed increase 30min after exercise, decreasing slightly in the final stage. Negative correlation between bicarbonate ion and chloride ion were determined. It was concluded that exercise tests are useful for the determination of acid-base balance and osmotic balance, and their main role is to evaluate the athletic ability of horses.Considering that chloride ion excretion and metabolic adjustments of potassium ion and bicarbonate ion are superior to water loss, compared to the normal osmolarity of blood serum. The results found can be used to structure an adequate replacement program of electrolytes lost in sweat.

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Potassium: friend or foe?

Cited by 37 publications

References 117 publications

WNK4 kinase is a physiological intracellular chloride sensor

WNK4 kinase is a physiological intracellular chloride sensor

Essential role of Kir5.1 channels in renal salt handling and blood pressure control

Effects of exercise on cations/anions in blood serum of English Thoroughbred horses

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