Evidence map›Paper›PMID 10718749›Full record

ArticleThe Journal of physiology2000

Intracellular cyclic AMP inhibits native and recombinant volume-regulated chloride channels from mammalian heart.

M Nagasaki, L Ye, D Duan, B Horowitz, J R Hume

Open access · greenAbstract read
In one paragraph

Article in The Journal of physiology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Chloride channelopathies of ClC-2.International journal of molecular sciences · 2013
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

M NagasakiDepartment of Physiology and Cell Biology, University of Nevada, School of Medicine, Reno, NV 89557-0046, USA.
L Ye
D Duan
B Horowitz
J R Hume
University of Nevada, Reno · US

Funding

CHLORIDE CHANNELS IN HEARTR01HL052803 · NHLBI · UNIVERSITY OF NEVADA RENO · PI HUME, JOSEPH R · 1996 to 2000
$227k
NHLBI NIH HHS HL52803
6 · The paper itself

Abstract

1. ClC-3 encodes a volume-regulated Cl- channel (ICl,vol) in heart. We studied the regulation of native and recombinant cardiac ICl,vol by intracellular cyclic AMP (cAMPi). 2. Symmetrical high Cl- concentrations were used to effectively separate outwardly rectifying ICl,vol from other non-rectifying Cl- currents, such as the cystic fibrosis transmembrane conductance regulator (CFTR) and Ca2+-activated Cl- currents (ICl,CFTR and ICl,Ca, respectively), which are concomitantly expressed in cardiac myocytes. 3. 8-Bromo-cyclic AMP (8-Br-cAMP) significantly inhibited ICl,vol in most guinea-pig atrial myocytes. In approximately 30 % of the atrial myocytes examined, 8-Br-cAMP increased macroscopic Cl- currents. However, the 8-Br-cAMP-stimulated difference currents exhibited a linear current-voltage (I-V ) relation, consistent with activation of ICl,CFTR, not ICl,vol. 4. In canine atrial myocytes, isoprenaline (1 microM) consistently reduced ICl,vol in Ca2+-free hypotonic bath solutions with strong intracellular Ca2+ (Ca2+i) buffering. In Ca2+-containing hypotonic bath solutions with weak Ca2+i buffering, however, isoprenaline increased net macroscopic Cl- currents. Isoprenaline-stimulated difference currents were not outwardly rectifying, consistent with activation of ICl,Ca, not ICl, vol. 5. In NIH/3T3 cells transfected with gpClC-3 (the gene encoding ICl,vol), 8-Br-cAMP consistently inhibited ICl,ClC-3. These effects were prevented by a protein kinase A (PKA) inhibitor, KT5720, or by mutation of a single consensus protein kinase C (PKC) phosphorylation site (S51A) on the N-terminus of ClC-3, which also mediates PKC inhibition of ICl,ClC-3. 6. We conclude that cAMPi causes inhibition of ICl,vol in mammalian heart due to cross-phosphorylation of the same PKC consensus site on ClC-3 by PKA. Our results suggest that contamination of macroscopic ICl,vol by ICl,CFTR and/or ICl,Ca may account for some of the inconsistent and controversial effects of cAMPi on ICl,vol previously reported in native cardiac myocytes.

Indexed as

3T3 Cells8-Bromo Cyclic Adenosine MonophosphateAdenosine MonophosphateAnimalsChloride ChannelsCyclic AMP-Dependent Protein KinasesDogsFemaleGuinea PigsHeart AtriaIntracellular MembranesIsoproterenolMaleMiceMyocardiumPhosphorylation8-Bromo Cyclic Adenosine MonophosphateAdenosine MonophosphateChloride ChannelsClC-3 channelCyclic AMP-Dependent Protein KinasesIsoproterenolProtein Kinase CRecombinant Proteins

Identifiers

PMID10718749
PMCPMC2269833
OpenAlexW2157659129

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.