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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of cell shrinkage on whole-cell currents of M-1 mouse cortical collecting duct cells. Addition of 100 mM sucrose to an isotonic NaCl bath solution induced cell shrinkage and increased whole-cell currents within 5-10 min by approximately 12-fold. The effect was reversible upon return to isotonic solution and could also be elicited by adding 100 mM urea or 50 mM NaCl. Replacement of bath Na+ by K+, Cs+, Li+, or Rb+ did not significantly affect the stimulated inward current, but replacement by N-methyl-D-glucamine reduced it by 88.1 +/- 1.3% (n = 34); this demonstrates that hypertonicity activates a nonselective alkali cation conductance. The activation was independent of extra- and intracellular Ca2+, but 1 or 10 mM ATP in the pipette suppressed it in a concentration-dependent manner, indicating that intracellular ATP levels may modulate the degree of channel activation. Flufenamic acid (0.1 mM) and gadolinium (0.1 mM) inhibited the stimulated current by 68.7 +/- 5.9% (n = 9) and 32.4 +/- 11.7% (n = 6), respectively, whereas 0.1 mM amiloride had no significant effect. During the early phase of hypertonic stimulation single-channel transitions could be detected in whole-cell current recordings, and a gradual activation of 30 and more individual channels with a single-channel conductance of 26.7 +/- 0.4 pS (n = 29) could be resolved. Thus, we identified the nonselective cation channel underlying the shrinkage-induced whole-cell conductance that may play a role in volume regulation.
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PMID:Hypertonicity activates nonselective cation channels in mouse cortical collecting duct cells. 754 4

We recently reported that M-1 mouse cortical collecting duct cells show nonselective cation (NSC) channel activity (Proc. Natl. Acad. Sci. USA 89:10262-10266, 1992). In this study, we further characterize the M-1 NSC channel using single-channel current recordings in excised inside-out patches. The M-1 NSC channel does not discriminate between Na+, K+, Rb+, Cs+, and Li+. It has a linear I-V relation with a conductance of 22.7 +/- 0.5 pS (n = 78) at room temperature. The Pcation/P(anion) ratio is about 60 and there is no measurable conductance for NMDG, Ca2+, Ba2+, and Mn2+. Cytoplasmic calcium activates the M-1 NSC channel at a threshold of 10(-6) M and depolarization increases channel activity (NPo). Cytoplasmic application of adenine nucleotides inhibits the M-1 NSC channel. At doses of 10(-4) M and 10(-3) M, ATP reduces NPo by 23% and 69%, respectively. Furthermore, since ADP (10(-3) M) reduces NPo by 93%, the inhibitory effect of adenine nucleotides is not dependent on the presence of a gamma-phosphoryl group and therefore does not involve protein phosphorylation. The channel is not significantly affected by 8-Br-cGMP (10(-4) M) or by cGMP-dependent protein kinase (10(-7) M) in the presence of 8-Br-cGMP (10(-5) M) and ATP (10(-4) M). The NSC channel is not sensitive to amiloride (10(-4) M cytoplasmic and/or extracellular) but flufenamic acid (10(-4) M) produces a voltage-dependent block, reducing NPo by 35% at depolarizing voltages and by 80% at hyperpolarizing voltages. We conclude that the NCS channel of M-1 mouse cortical collecting duct cells belongs to an emerging family of calcium-activated and nucleotide-sensitive nonselective cation channels. It does not contribute to amiloride-sensitive sodium absorption and is unlikely to be a major route for calcium entry. The channel is normally quiescent but may be activated under special physiological conditions, e.g., during volume regulation.
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PMID:A calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells. 756 35

The role of membrane-bound protein serine/threonine phosphatases (PP) in modulating the renal ATP-sensitive K+ (KATP) channel was examined using the patch-clamp technique in principal cells of rat cortical collecting duct. In the absence of ATP, channel activity rapidly (11.2 s) declines (channel "rundown") upon excision of the membrane patches into control bath solutions (1 mM Mg2+, Ca2+ free). Both orthovanadate (5 mM), a broad-spectrum inhibitor of phosphatases except for Ca(2+)-dependent PP (PP-2B), and okadaic acid (OA, 1 microM), a potent inhibitor of PP types 1 and 2A (PP-1 and PP-2A), significantly slowed channel rundown. Removal of Mg2+ from the bath also slowed the rundown process. Incubation of cells with OA in the absence of Mg2+ or with orthovanadate in ATP-free solution maintained channel activity at levels of approximately 70% of control values for 3 min after membrane excision. In contrast, Ca2+ (0.1 mM) and calmodulin (1 microM) in the presence of 1 mM Mg2+, a condition in which PP-2B is stimulated, had no significant effect on the channel activity that persisted in the presence of OA and orthovanadate. Application of exogenous PP-2A (1 U/ml) to the cytosolic side of membrane in inside-out patches significantly inhibited channel activity to 35.0% of control, but the inhibitory-effects of PP-1 (1 U/ml) and PP-2B (20 micrograms/ml) were minor. These results suggest that rundown of the renal KATP channel after membrane excision results mainly from dephosphorylation of the channel or an associated protein by membrane-bound phosphatases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of ATP-sensitive K+ channel by membrane-bound protein phosphatases in rat principal tubule cell. 757 84

The inwardly rectifying, ATP-sensitive K+ channel (ROMK) was localized by in situ hybridization in the rat kidney. Tissue in situ hybridization revealed that transcripts encoding the ROMK channel were expressed predominantly in cortical and outer medullary nephron segments. The localization of ROMK mRNA to specific nephron segments was assessed by hybridization of isolated nephron segments with an ROMK-specific probe (single segment in situ hybridization). ROMK mRNA was present in cortical and medullary thick ascending limb, distal tubule, and cortical and outer medullary collecting ducts, but not in proximal tubule. A weak hybridization was observed with inner medullary collecting ducts. To confirm these results, serial cryosections were alternatively stained by hybridization histochemistry for ROMK mRNA or by immunocytochemistry using antibodies specific for S1, S2, or S3 proximal tubular segments. Tubular cells that displayed immunoreactivity with the proximal tubular segment-specific antibodies showed little, if any, ROMK message. In addition, using an in situ hybridization and immunocytochemistry double-labeling technique, ROMK transcripts and vitamin D-dependent calcium-binding protein were shown to colocalize to the distal tubule (distal convoluted tubule and connecting tubule). The overall nephron localization of ROMK mRNA shown in these studies is consistent with the possibility that this novel channel may represent the low-conductance ATP-sensitive K+ channel that has been identified in apical membranes of thick limb and collecting duct segments and is believed to participate in K+ secretion.
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PMID:ROMK inwardly rectifying ATP-sensitive K+ channel. I. Expression in rat distal nephron segments. 761 53

Properties of ion channels of the cortical collecting duct (CCD) and their relevance for the macroscopic conductances are discussed. Although the regulation of the Na+ conductance by various hormones is widely studied, the relevant Na+ channel appears to be extremely difficult to be detected in the intact preparation. Three different K+ channels with slope conductances of about 30, 140 and 80 pS (excised, 145 mmol/l KCL and 145 mmol/l NaCl on both sides of the membrane) have been found in principal cells of the CCD so far. The first two channels are located in the luminal, the latter one in the basolateral membrane. The two luminal channels are highly sensitive to the cytosolic pH and are also inhibited by cytosolic ATP. The small luminal K+ channel, highly active on the cell, is most likely responsible for K+ secretion. The large luminal K+ channel is involved in the volume regulation. The basolateral K+ channel, again highly active on the cell, is probably responsible for the recirculation of K+ across this membrane. The physiological role of the observed Cl- channels is still unknown.
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PMID:Regulation of ion channels in the cortical collecting duct. 768 44

4-Pentenoate (4P) is a short-chain fatty acid which causes a complete renal Fanconi syndrome. We have examined the mechanism of 4P toxicity along the nephron after a prolonged (30 min) exposition of isolated renal tubular segments to this agent. In proximal tubules, 4P inhibited the activity of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, and beta-oxidation, but not in thick ascending limb or inner medullary collecting duct tubules in suspension. These proximal effects were accompanied by a marked oxidation of the proximal redox state, with a fall in the tissue respiration and a low content of ATP. The acetyl-CoA content of proximal tubules was simultaneously reduced. Butyrate, acetate, hexanoate or octanoate did not exert these effects. In proximal tubules the metabolism of 4P led to the tissue accumulation of 3-keto-4-pentenoyl-CoA, a known unspecific inhibitor of metabolic oxidation. This metabolite was not detectable in thick ascending limbs which metabolized 4P rapidly. No metabolism of 4P was noted in collecting ducts. We conclude that beta-oxidation probably differs in proximal and thick ascending limb tubules, allowing 4P metabolism to exert a specific toxicity in proximal tubules. A selective proximal defect in energy metabolism probably explains the Fanconi syndrome observed with exposition to 4P.
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PMID:Heterogeneous metabolism and toxicity of 4-pentenoate along the dog nephron. 768 41

Enzymatic and microperfusion studies have indicated that an ATP-dependent H+/K+ exchange process is present in the collecting duct of the mammalian kidney. Immunochemical staining has also provided evidence for expression of a gastric-type H(+)-K+ adenosine triphosphatase (H(+)-K(+)-ATPase). Rat kidney mRNA was probed with use of the polymerase chain reaction (PCR) to determine the presence of an H(+)-K(+)-ATPase. cDNA made with mRNA isolated from the kidneys of rats maintained on a low-K diet was used as template in PCR reactions with primers encompassing the cDNA sequence of the alpha-subunit of the gastric H(+)-K(+)-ATPase and the 5' and 3' ends of the colonic H(+)-K(+)-ATPase. The resulting products, 300-700 bp in size, hybridized with probes directed against either the gastric or colonic sequences of the H(+)-K(+)-ATPase. Sequencing of the individual PCR products showed identity with the appropriate regions of the alpha-subunits of the gastric H(+)-K(+)-ATPase and colonic H(+)-K(+)-ATPase. These data indicate that the rat kidney expresses mRNAs encoding both gastric and colonic H(+)-K(+)-ATPases.
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PMID:Expression of gastric and colonic H(+)-K(+)-ATPase in the rat kidney. 773 14

Recent studies in a variety of cell types have revealed several receptor subtypes that bind ATP and trigger increases in intracellular Ca2+ concentration ([Ca2+]i). The present studies were aimed at determining whether similar receptors are present in the rat terminal inner medullary collecting duct (IMCD). [Ca2+]i was measured using fura 2 in tubules dissected from collagenase-treated rat kidneys. ATP (1-100 microM) caused a rapid increase in [Ca2+]i with a prolonged late phase after an initial peak. A similar rise was observed in tubules exposed to UTP or to the poorly hydrolyzable analogue, adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S). In contrast, agonists that bind P2x, P2y, P2z, and P2t purinergic receptors did not affect [Ca2+]i. Removal of extracellular Ca2+ inhibited the response to ATP by approximately 50% with obliteration of the late phase. Furthermore, indomethacin attenuated the rise in [Ca2+]i produced by ATP. Adenosine analogues also increased [Ca2]i apparently by binding to distinct adenosine receptors rather than to the ATP receptor. We conclude that there is a nucleotide receptor in the rat terminal IMCD, which, when occupied, mobilizes intracellular Ca2+.
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PMID:Extracellular ATP increases intracellular calcium in rat terminal collecting duct via a nucleotide receptor. 781 Jul 8

The interaction of K+ and NH+4 on the basolateral membrane of cultured rat inner medullary collecting duct cells (IMCD) was explored using 86Rb+ as a K+ congener. Ouabain addition decreased Rb+ uptake to 22.0 +/- 2.6% of control. Possible ouabain-sensitive NH+4 transport was therefore explored. Replacement of N-methyl-D-glucamine chloride with NH4Cl or KCl decreased both total and ouabain-sensitive Rb+ uptake. This inhibition of Rb+ uptake by NH+4 was not due to changes in intracellular pH or differences in cell viability. We conclude that NH+4 competes with K+ for binding on the Na(+)-K(+)-adenosinetriphosphatase (ATPase). An inhibitory constant (Ki) for NH+4 of 11.0 +/- 1.6 and a Michaelis constant (Km) for K+ of 1.9 +/- 0.7 mM were measured. To extend these observations, NH+4 was tested as a substrate for ouabain-sensitive ATPase activity in native permeabilized IMCD cells. With 20 mM K+, activity was 202 +/- 73 nmol ATP hydrolyzed.min-1.mg protein-1, and with 20 mM NH+4, activity was 259 +/- 81 nmol ATP hydrolyzed.min-1.mg protein-1. Thus NH+4 substitution for K+ on the Na(+)-K(+)-ATPase is a likely mechanism for NH+4 uptake by the IMCD.
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PMID:NH+4 transport mediated by Na(+)-K(+)-ATPase in rat inner medullary collecting duct. 794 62

The inner medullary collecting duct (IMCD) in vivo has the capacity to either secrete or reabsorb K+. However, a selective K+ conductance has not been described previously in the IMCD. In the present study, the patch-clamp method was used to determine the presence and properties of K(+)-selective channels in the apical membrane of the inner medullary collecting duct cell line, mIMCD-3. Two types of K(+)-selective channels were observed in both cell-attached and excised patches. The most predominant K+ channel, a smaller conductance K+ channel (SK), was present in cell-attached patches with 140 mM KCl (high bath K+) but not with 135 mM NaCl plus 5 mM KCl (low bath K+) in the bathing solution. The single-channel conductance of SK was 36 pS with inward currents and 29 pS with outward currents in symmetrical 140 mM KCl. SK was insensitive to both voltage and Ca2+. However, SK was inhibited significantly by millimolar concentrations of ATP in excised patches. A second K(+)-selective channel [a larger K+ channel (BK)] displayed a single-channel conductance equal to 132 pS with inward currents and 90 pS with outward currents in symmetrical 140 mM KCl solutions. BK was intermittently activated in excised inside-out patches by Mg(2+)-ATP in concentrations from 1 to 5 mM. With complete removal of Mg2+, BK was insensitive to ATP. BK was also insensitive to potential and Ca2+ and was observed in cell-attached patches with 140 mM KCl in the bath solution. Both channels were blocked reversibly by 1 mM Ba2+ from the intracellular surface but not by external Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ATP-sensitive K(+)-selective channels of inner medullary collecting duct cells. 809 63


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