Activation of K+ channels in renal medullary vesicles by cAMP-dependent protein kinase

Reeves, W. Brian; McDonald, Gregory A.; Mehta, Pramod S.; Andreoli, Thomas E.

doi:10.1007/bf01870791

Cited by 42 publications

(19 citation statements)

References 30 publications

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“…In the case of bumetanide, both amiloride and forskolin inhibit this increase in K+ concentration and so could suggest that this is a ductal phenomenon. It is also possible that a change in intracellular pH or cyclic AMP concentration caused by amiloride and forskolin could inhibit apical K+ channels (Brown, Loo & Wright, 1988;Reeves, McDonald, Mehta & Andreoli, 1989). Clearly, it is not possible to reach a definitive conclusion regarding this phenomenon on the basis of present evidence.…”

Section: The Effects Of Bariumcontrasting

confidence: 49%

The effects of bumetanide, amiloride and Ba2+ on fluid and electrolyte secretion in rabbit salivary gland.

Lau

Howorth

Case

1990

The Journal of Physiology

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SUMMARY1. In order to distinguish between models of anion secretion, the effects of transport inhibitors on saliva flow rate and electrolyte composition were studied during the plateau phase of secretion in rabbit mandibular salivary glands.2. Bumetanide, an inhibitor of Na+,K+,2CP-co-transport, inhibited flow rate (by 60%) and reduced Cl-concentration. K+ and HC03-concentrations were increased. Forskolin, an adenylate cyclase activator which inhibits ductal transport, did not significantly affect this pattern of changes.3. Amiloride, used at concentrations that would inhibit Na+-H+ exchange, inhibited flow rate (by 30 %). Cl-concentration was initially increased before subsequently decreasing at the same time as HC03-concentration increased. These concentration changes can probably be attributed to ductal transport. When amiloride was applied to glands perfused with nominally HCO3--free solutions, inhibition of flow rate was rapid and almost complete.4. When amiloride and bumetanide were both present in the perfusate, flow rate was inhibited by 92%. The pattern of electrolyte changes was not significantly different from that observed in the presence of bumetanide alone.5. Inhibition of K+ channel activity using Ba2+ also inhibited flow rate. Cl--concentration was increased as was K+ concentration. HC03-concentration was not increased.6. The anion exchange inhibitor DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid) had no effect on either flow rate or electrolyte concentration. It did, however, elicit secretion in the absence of acetylcholine.7. The data suggest that Na+-H+ and Cl--HCO3-exchangers are unlikely to be involved in fluid and electrolyte secretion in these glands as suggested by some authors. Most of the data can be explained by postulating the existence of nonspecific anion channels in the apical membranes of the acinar cells.

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Section: The Effects Of Bariumcontrasting

confidence: 49%

The effects of bumetanide, amiloride and Ba2+ on fluid and electrolyte secretion in rabbit salivary gland.

Lau

Howorth

Case

1990

The Journal of Physiology

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“…The effect of vasopressin is mediated by a cAMP-dependent pathway because application of cAMP analogs mimics the effect of vasopressin (21). That vasopressin stimulates the apical K ϩ conductance in the TAL has been reported in several studies using microelectrodes and vesicles (23,24). ROMK channels have three putative serine PKA phosphorylation sites (2), and Xu et al (25) have shown that these sites can be phosphorylated in vitro.…”

Section: Discussionmentioning

confidence: 99%

The A kinase anchoring protein is required for mediating the effect of protein kinase A on ROMK1 channels

Ali

Chen

et al. 1998

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

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In the present study, we have used the twoelectrode voltage-clamp and patch-clamp techniques to study the effects of forskolin and cAMP on the ROMK1 channels, which are believed to be the native K ؉ secretory channels in the kidney. Addition of 1 M forskolin or 100 M 8-bromocAMP, within 10 min, has no significant effect on the current of ROMK1 channels expressed in Xenopus oocytes. In contrast, application of 1 M forskolin, within 3 min, significantly increased whole-cell K ؉ current by 35%, when ROMK1 channels were coexpressed with the A kinase anchoring protein AKAP79, which was cloned from neuronal tissue. Two lines of evidence indicate that the effect of forskolin is mediated by a cAMP-dependent pathway: (i) Addition of 100 M 8-bromo-cAMP mimics the effect of forskolin and (ii) the effect of forskolin and cAMP is not additive. That AKAP is required for the effect of cAMP is further supported by experiments in which addition of ATP (100 M) and cAMP (100 M) restored the activity of run-down ROMK1 channels in inside-out patches in oocytes that coexpressed ROMK1 and AKAP79 but not in those that expressed ROMK1 alone. Moreover, when we used RII, the regulatory subunit of type II protein kinase A, in an overlay assay, we identified a RIIbinding protein in membranes obtained from the kidney cortex but not in membranes from oocytes. This suggests that the insensitivity of ROMK1 channels to forskolin and cAMP is due to the absence of AKAPs. We conclude that AKAP may be a critical component that mediates the effect of protein kinase A on the ROMK channels in the kidney.We have previously demonstrated that stimulation of protein kinase A (PKA) activates the ROMK-like K ϩ secretory channel in the thick ascending limb (TAL) and cortical collecting duct (CCD) (1). The ROMK channel is an important member of the family of inwardly rectifying K ϩ channels with two transmembrane segments (2). Several lines of evidence indicate that the ROMK channels are closely related to the renal low-conductance ATP-sensitive K ϩ channels located in the TAL and in the CCD (1). (i) In situ hybridization has shown the presence of mRNA encoding ROMK channels in the CCD and the TAL. Immunocytochemical studies have further revealed the presence of ROMK channels in the apical membrane where renal ATP-sensitive K ϩ channels have been identified (3, 4). (ii) The conductance (30-40 pS) and kinetics of ROMK channels expressed in oocytes are identical to those of the native low-conductance ATP-sensitive K ϩ channels in the CCD and the TAL (5, 6). (iii) Both the low-conductance ATP-sensitive K ϩ channel and the ROMK channel are stimulated by PKA-induced phosphorylation (7).Recently, it has been suggested that the A kinase anchoring protein (AKAP) is required for mediating PKA-induced phosphorylation of cellular proteins (8 -10). AKAPs are involved in the localization of the type II isoform of PKA in a variety of cell membranes (9). More than 70% of the type II of PKA is bound to the cell membrane (11). Several studies have recently shown that A...

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“…Alternatively, we have observed that, in apical medullary vesicles, the adenylate cyclase cascade produces a direct activation of K + channels [23]; and that, in intact mTALH segments, blockade of apical membrane Na + : K + : 2C1-entry with furosemide abolishes detectable ADH-dependent increases in basolateral C1-conductance [19]. Thus we have proposed that, in mTALH segments, ADH increases the rate of apical membrane salt entry, and that the attendant rise in basolateral C1-conductance is due to a rise in intracellular C1-activity [19].…”

Section: Introductionmentioning

confidence: 95%

“…22Na+ UPTAKE Bumetanide-sensitive, (K++C1-)-dependent 22Na+ uptake was determined in triplicate as described previously [23] after loading the vesicles with solution H. A 20 /xl-aliquot of vesicles was added to 25 ~*1 of solution I containing 0.9 mM =Na + (32/xC/ml), 1.8 mM amiloride, and either 0 or 1.8 mM bumetanide, This re- suited in a final outside solution containing 1 mM amiloride with or without 1 mM bumetanide (Solution J, Table 1), which has hypertonic relative to the inside solution. After 5 sec, 1.5 ml of a cold stop solution containing 150 mM KNO3 and 20 mM triethanolamine was added and the vesicles were filtered and then washed four times with 1.5 ml of the cold stop solution.…”

Section: C1 Uptakementioning

confidence: 99%

Cl− transport in basolateral renal medullary vesicles: I. Cl− transport in intact vesicles

1990

Self Cite

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This paper provides the results of studies which characterized conductive 36Cl- flux in basolaterally enriched membrane vesicles prepared from rabbit renal outer medulla. Conductive 36Cl- uptake was studied under two different experimental conditions. In the first, 36Cl- flux was driven by an inside positive voltage created with oppositely directed Cl- and gluconate gradients. In the second, an inwardly direct K+ gradient was used to drive 36Cl- uptake. By these two methods, voltage-sensitive 36Cl- uptake was shown to comprise about 45 and 65%, respectively, of the initial rates of total 36Cl- flux. Separate paired studies demonstrated that the conductive 36Cl- uptake was inhibited by the Cl- channel blocker diphenylamine-2-carboxylate (DPC) with an IC50 for DPC of 154 microM. The voltage-dependent 36Cl- uptake had an activation energy of 6.4 kcal/mole. This 36Cl- conductance had an anion selectivity sequence of I- greater than Cl- greater than or equal to NO3- much greater than gluconate.

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Activation of K+ channels in renal medullary vesicles by cAMP-dependent protein kinase

Cited by 42 publications

References 30 publications

The effects of bumetanide, amiloride and Ba2+ on fluid and electrolyte secretion in rabbit salivary gland.

The effects of bumetanide, amiloride and Ba2+ on fluid and electrolyte secretion in rabbit salivary gland.

The A kinase anchoring protein is required for mediating the effect of protein kinase A on ROMK1 channels

Cl− transport in basolateral renal medullary vesicles: I. Cl− transport in intact vesicles

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