Targeting colonic BK channels: A novel therapeutic strategy against hyperkalemia in chronic kidney disease

Kazama, Itsuro; Shoji, Michiko

doi:10.1016/j.nefro.2023.01.001

Cited by 2 publications

(1 citation statement)

References 9 publications

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“…While DEX is primarily used for its anti-inflammatory effects, it can also have some mineralocorticoid (aldosterone-like) effects at higher doses or with prolonged use. DEX can bind to mineralocorticoid receptors (MRs) in the same way as aldosterone does, and it exerts similar effects on the kidneys [ 36 , 37 , 38 ]. However, the immediate stimulation of BK Ca channels by DEX or other glucocorticoids might partly be responsible for its rapid inhibition of hormone release because such an effect facilitates Ca 2+ -induced feedback hyperpolarization and prevents voltage-activated Ca 2+ entry [ 9 , 31 , 38 , 39 ].…”

Section: Dexamethasone (9α-fluoro-11β17α21-trihydroxy-16α-methylpregn...mentioning

confidence: 99%

Investigating the Impact of Selective Modulators on the Renin–Angiotensin–Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents

Lu,

2023

IJMS

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The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in maintaining various physiological processes in the body, including blood pressure regulation, electrolyte balance, and overall cardiovascular health. However, any compounds or drugs known to perturb the RAAS might have an additional impact on transmembrane ionic currents. In this retrospective review article, we aimed to present a selection of chemical compounds or medications that have long been recognized as interfering with the RAAS. It is noteworthy that these substances may also exhibit regulatory effects in different types of ionic currents. Apocynin, known to attenuate the angiotensin II-induced activation of epithelial Na+ channels, was shown to stimulate peak and late components of voltage-gated Na+ current (INa). Esaxerenone, an antagonist of the mineralocorticoid receptor, can exert an inhibitory effect on peak and late INa directly. Dexamethasone, a synthetic glucocorticoid, can directly enhance the open probability of large-conductance Ca2+-activated K+ channels. Sparsentan, a dual-acting antagonist of the angiotensin II receptor and endothelin type A receptors, was found to suppress the amplitude of peak and late INa effectively. However, telmisartan, a blocker of the angiotensin II receptor, was effective in stimulating the peak and late INa along with a slowing of the inactivation time course of the current. However, telmisartan’s presence can also suppress the erg-mediated K+ current. Moreover, tolvaptan, recognized as an aquaretic agent that can block the vasopressin receptor, was noted to suppress the amplitude of the delayed-rectifier K+ current and the M-type K+ current directly. The above results indicate that these substances not only have an interference effect on the RAAS but also exert regulatory effects on different types of ionic currents. Therefore, to determine their mechanisms of action, it is necessary to gain a deeper understanding.

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Section: Dexamethasone (9α-fluoro-11β17α21-trihydroxy-16α-methylpregn...mentioning

confidence: 99%

Investigating the Impact of Selective Modulators on the Renin–Angiotensin–Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents

Lu,

2023

IJMS

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Sodium bicarbonate and salbutamol facilitate recovery from hyperkalemia-induced electrocardiogram abnormalities in bullfrog hearts

AZUMA,

KUWANA,

NARISAWA

et al. 2023

The Journal of Veterinary Medical Science

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Hyperkalemia is a common electrolyte abnormality frequently complicated with chronic kidney disease. By injecting potassium chloride (KCl) solutions intravenously into bullfrogs, we reproduced typical electrocardiogram (ECG) abnormalities of hyperkalemia in the frog hearts, such as the peaked T waves and the widening of QRS complexes. Simultaneous recordings of cardiac action potentials showed morphological changes that synchronized with those of ECG. After 100 mM KCl injection, the widened QRS complexes continued for a while and gradually restored to their baseline widths. However, pre-treatment with sodium bicarbonate or salbutamol, which directly or indirectly stimulates Na + /K + -ATPase activity, significantly facilitated the recovery from the widened QRS duration, indicating the transcellular movement of potassium ions from the extracellular fluid into the intracellular stores.

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Targeting colonic BK channels: A novel therapeutic strategy against hyperkalemia in chronic kidney disease

Cited by 2 publications

References 9 publications

Investigating the Impact of Selective Modulators on the Renin–Angiotensin–Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents

Investigating the Impact of Selective Modulators on the Renin–Angiotensin–Aldosterone System: Unraveling Their Off-Target Perturbations of Transmembrane Ionic Currents

Sodium bicarbonate and salbutamol facilitate recovery from hyperkalemia-induced electrocardiogram abnormalities in bullfrog hearts

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