miR-363-5p- and IL-34-mediated modulation of pacemaker channel, HCN4, on iPSC-CM: Translation into the human sinus node microenvironment.

Background: The human sinus node (SN) contains cardiac fibroblasts and resident macrophages, with microRNAs (miRNAs) and interleukins as regulators of SN function. However, the mechanisms by which they influence heart rate remain unclear.

Objective: This study aimed to investigate the SN microenvironment, encompassing miRNAs, interleukins, macrophages, and fibroblasts and modulating induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and hence beating rate.

Kir4.1/Kir5.1 of distal convoluted tubule is required for short-term angiotensin-II-induced stimulation of Na-Cl cotransporter.

Angiotensin-II (Ang-II) perfusion stimulates inwardly-rectifying potassium channels 4.1 and 5.1 (Kir4.

Role of Kir4.1/Kir5.1 in mediating Angiotensin-II (Ang-II)-induced stimulation of thiazide-sensitive Na-Cl cotransporter.

Background: Angiotensin-II (Ang-II) perfusion stimulates Kir4.1/Kir5.1 in the distal-convoluted-tubule (DCT) and thiazide-sensitive Na-Cl-cotransporter (NCC).

Angiotensin II-Type-1a Receptor and Renal K + Wasting during Overnight Low-Na + Intake.

Key Points: Angiotensin II–type-1a-receptor in the distal convoluted tubule (DCT) plays a role in regulating sodium transport in the DCT. Angiotensin II–type-1a-receptor in the DCT plays a role in maintaining potassium homeostasis during sodium restriction.

Background: Chronic angiotensin II perfusion stimulates Kir4.

Role of calcineurin in regulating renal potassium (K) excretion: Mechanisms of calcineurin inhibitor-induced hyperkalemia.

Calcineurin, protein phosphatase 2B (PP2B) or protein phosphatase 3 (PP3), is a calcium-dependent serine/threonine protein phosphatase. Calcineurin is widely expressed in the kidney and regulates renal Na and K transport. In the thick ascending limb, calcineurin plays a role in inhibiting NKCC2 function by promoting the dephosphorylation of the cotransporter and an intracellular sorting receptor, called sorting-related-receptor-with-A-type repeats (SORLA), is involved in modulating the effect of calcineurin on NKCC2.

mTORc2 in Distal Convoluted Tubule and Renal K + Excretion during High Dietary K + Intake.

Key Points: High K stimulates mechanistic target of rapamycin complex 2 (mTORc2) in the distal convoluted tubule (DCT). Inhibition of mTORc2 decreased the basolateral Kir4.1/Kir5.

[Recording and identification of depolarization-activated current in intercalated cells].

The depolarization-activated current of intercalated cells in the distal nephron was detected for the first time, and the type of ion channel mediating the current was identified based on electrophysiological and pharmacological properties. The whole-cell current of distal nephron in kidney of C57BL/6J mice was recorded by Axon MultiClamp 700B patch-clamp system, and the effects of several K channel inhibitors on the depolarization-activated current in intercalated cells were observed. In addition, the immunofluorescence technique was used to investigate the localization of the channel in intercalated cells.

Adenosine stimulates the basolateral 50 pS K channel in renal proximal tubule via adenosine-A1 receptor.

The basolateral potassium channels play an important role in maintaining the membrane transport in the renal proximal tubules (PT) and adenosine receptors have been shown to regulate the trans-epithelial Na absorption in the PT. The aim of the present study is to explore whether adenosine also regulates the basolateral K channel of the PT and to determine the adenosine receptor type and the signaling pathway which mediates the effect of adenosine on the K channel. We have used the single channel recording to examine the basolateral K channel activity in the proximal tubules of the mouse kidney.

Alkali and Heavy Metal Copoisoning Resistant Catalytic Reduction of NO via Liberating Lewis Acid Sites.

The catalyst deactivation caused by the coexistence of alkali and heavy metals remains an obstacle for selective catalytic reduction of NO with NH. Moreover, the copoisoning mechanism of alkali and heavy metals is still unclear. Herein, the copoisoning mechanism of K and Cd was revealed from the adsorption and variation of reaction intermediates at a molecular level through time-resolved spectroscopy combined with theoretical calculations.

Macrolides selectively inhibit mutant KCNJ5 potassium channels that cause aldosterone-producing adenoma.

Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce the salt-retaining steroid hormone aldosterone and cause millions of cases of severe hypertension worldwide. Either of 2 somatic mutations in the potassium channel KCNJ5 (G151R and L168R, hereafter referred to as KCNJ5MUT) in adrenocortical cells account for half of APAs worldwide. These mutations alter channel selectivity to allow abnormal Na+ conductance, resulting in membrane depolarization, calcium influx, aldosterone production, and cell proliferation.

ENaC and ROMK activity are inhibited in the DCT2/CNT of TgWnk4 mice.

Mice transgenic for genomic segments harboring PHAII (pseudohypoaldosteronism type II) mutant Wnk4 (with-No-Lysine kinase 4) (TgWnk4) have hyperkalemia which is currently believed to be the result of high activity of Na-Cl cotransporter (NCC). This leads to decreasing Na delivery to the distal nephron segment including late distal convoluted tubule (DCT) and connecting tubule (CNT). Since epithelial Na channel (ENaC) and renal outer medullary K channel (ROMK or Kir4.

PGF regulates the basolateral K channels in the distal convoluted tubule.

Our aim is to examine the role of PGF receptor (FP), a highly expressed prostaglandin receptor in the distal convoluted tubule (DCT) in regulating the basolateral 40-pS K channel. The single-channel studies demonstrated that PGF had a biphasic effect on the 40-pS K channel in the DCT-PGF stimulated at low concentrations (less than 500 nM), while at high concentrations (above 1 µM), it inhibited the 40-pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF (a metabolite of PGF) nor PGE was able to mimic the effect of PGF on the 40-pS K channel in the DCT.

Caveolin-1 regulates corneal wound healing by modulating Kir4.1 activity.

The expression of caveolin-1 (Cav1) in corneal epithelium is associated with regeneration potency. We used Cav1(-/-) mice to study the role of Cav1 in modulating corneal wound healing. Western blot and whole cell patch clamp were employed to study the effect of Cav1 deletion on Kir4.

Disruption of KCNJ10 (Kir4.1) stimulates the expression of ENaC in the collecting duct.

Kcnj10 encodes the inwardly rectifying K(+) channel 4.1 (Kir4.1) and is expressed in the basolateral membrane of late thick ascending limb, distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct (CCD).

Vasopressin-induced stimulation of the Na(+)-activated K(+) channels is responsible for maintaining the basolateral K(+) conductance of the thick ascending limb (TAL) in EAST/SeSAME syndrome.

The renal phenotype of EAST syndrome, a disease caused by the loss-of-function-mutations of Kcnj10 (Kir4.1), is a reminiscence of Gitelman's syndrome characterized by the defective function in the distal convoluted tubule (DCT). The aim of the present study is to test whether antidiuretic hormone (vasopressin)-induced stimulation of the Na(+)-activated 80-150pS K(+) channel is responsible for compensating the lost function of Kcnj10 in the thick ascending limb (TAL) of subjects with EAST syndrome.

Caveolin-1 Deficiency Inhibits the Basolateral K+ Channels in the Distal Convoluted Tubule and Impairs Renal K+ and Mg2+ Transport.

Kcnj10 encodes the inwardly rectifying K(+) channel Kir4.1 in the basolateral membrane of the distal convoluted tubule (DCT) and is activated by c-Src. However, the regulation and function of this K(+) channel are incompletely characterized.

KCNJ10 (Kir4.1) is expressed in the basolateral membrane of the cortical thick ascending limb.

The aim of the present study is to examine the role of Kcnj10 (Kir.4.1) in contributing to the basolateral K conductance in the cortical thick ascending limb (cTAL) using Kcnj10(+/+) wild-type (WT) and Kcnj10(-/-) knockout (KO) mice.

Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride.

Dietary potassium deficiency, common in modern diets, raises blood pressure and enhances salt sensitivity. Potassium homeostasis requires a molecular switch in the distal convoluted tubule (DCT), which fails in familial hyperkalemic hypertension (pseudohypoaldosteronism type 2), activating the thiazide-sensitive NaCl cotransporter, NCC. Here, we show that dietary potassium deficiency activates NCC, even in the setting of high salt intake, thereby causing sodium retention and a rise in blood pressure.

Kcnj10 is a major type of K+ channel in mouse corneal epithelial cells and plays a role in initiating EGFR signaling.

We used primary mouse corneal epithelial cells (pMCE) to examine the role of Kcnj10 in determining membrane K(+) conductance and cell membrane potential and in regulating EGF/TGFA release. Western blot, immunostaining, and RT-PCR detected the expression of Kcnj10 in mouse cornea. The single channel recording identified the 20-pS inwardly rectifying K(+) channels in pMCE of WT mice, but these channels were absent in Kcnj10(-/-).

KCNJ10 determines the expression of the apical Na-Cl cotransporter (NCC) in the early distal convoluted tubule (DCT1).

The renal phenotype induced by loss-of-function mutations of inwardly rectifying potassium channel (Kir), Kcnj10 (Kir4.1), includes salt wasting, hypomagnesemia, metabolic alkalosis and hypokalemia. However, the mechanism by which Kir.

Cyp2c44 epoxygenase in the collecting duct is essential for the high K+ intake-induced antihypertensive effect.

Cytochrome P-450, family 2, subfamily c, polypeptide 44 (Cyp2c44) epoxygenase metabolizes arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) in kidney and vascular tissues. In the present study, we used real-time quantitative PCR techniques to examine the effect of high salt or high K(+) (HK) intake on the expression of Cyp2c44, a major Cyp2c epoxygenase in the mouse kidney. We detected Cyp2c44 in the proximal convoluted tubule, thick ascending limb, distal convoluted tubule (DCT)/connecting tubule (CNT), and collecting duct (CD).

MicroRNA-194 (miR-194) regulates ROMK channel activity by targeting intersectin 1.

The aim of the study is to explore the role of miR-194 in mediating the effect of high-K (HK) intake on ROMK channel. Northern blot analysis showed that miR-194 was expressed in kidney and that HK intake increased while low-K intake decreased the expression of miR-194. Real-time PCR analysis further demonstrated that HK intake increased the miR-194 expression in the cortical collecting duct.

Inhibition of miR-205 impairs the wound-healing process in human corneal epithelial cells by targeting KIR4.1 (KCNJ10).

Purpose: The aim of the study was to test the hypotheses that injury stimulates the expression of miR-205, which in turn inhibits KCNJ10 channels by targeting its 3' UTR, thereby facilitating the wound-healing process in human corneal epithelial cells (HCECs).

Methods: A stem-loop qRT-PCR was used to examine the miR-205 expression. BrdU cell proliferation assay and wound scratch assay were applied to measure the effect of miR-205 mimic or antagomer in HCECs.