Cardiac ATP-sensitive K+ channel: A target for diadenosine 5′,5″-P1,P5-pentaphosphate

Aleksandar Jovanovic, Alexey E. Alekseev, Andre Terzic

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In numerous studies the intracellular mononucleotide-dependent gating of ATP-sensitive K+ (KATP) channels has been demonstrated. However, it is not known whether dinucleotide polyphosphates, a family of endogenous compounds structurally-related to ATP, could also modulate this ion conductance. Therefore, in the present study we assessed the direct effect of diadenosine 5′,5″-P1,P5-pentaphosphate (Ap5A) on cardiac KATP channel activity using the inside-out configuration of the patch-clamp technique. Addition of Ap5A (50 μM) to the internal side of membrane patches, excised from guinea-pig ventricular cells, strongly inhibited KATP channel activity. The estimated NPo (where N is the number of channels in the patch and Po the open probability of each channel) was 4.16 ± 0.50 in the absence and 0.85 ± 0.30 in the presence of Ap5A (50 μM). This effect of Ap5A was partially reversible, and the NP0 was 2.26 ± 0.60 after washout of Ap5A. Exposure of KATP channels to increasing concentrations of Ap5A revealed that the Ap5A-induced inhibition is concentration-dependent with the half-maximal effective concentration of 16 μM (Hill coefficient: 1.6). On the basis of these results, we conclude that Ap5A is a potent antagonist of the KATP channel activity. This represents a previously unrecognized property of Ap5A, as well as the discovery of a potentially novel endogenous ligand of myocardial KATP channels.

Original languageEnglish (US)
Pages (from-to)241-244
Number of pages4
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume353
Issue number2
StatePublished - 1996

Fingerprint

KATP Channels
Adenosine Triphosphate
P(1),P(5)-di(adenosine-5'-)pentaphosphate
Polyphosphates
Patch-Clamp Techniques
Guinea Pigs
Ions
Ligands
Membranes

Keywords

  • ATP-sensitive K channel
  • Cardiomyocyte
  • Channel gating
  • Diadenosine pentaphosphate
  • Diadenosine polyphosphates
  • Heart

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cardiac ATP-sensitive K+ channel : A target for diadenosine 5′,5″-P1,P5-pentaphosphate. / Jovanovic, Aleksandar; Alekseev, Alexey E.; Terzic, Andre.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 353, No. 2, 1996, p. 241-244.

Research output: Contribution to journalArticle

@article{20768d930c1941b3931e4b5900bcd210,
title = "Cardiac ATP-sensitive K+ channel: A target for diadenosine 5′,5″-P1,P5-pentaphosphate",
abstract = "In numerous studies the intracellular mononucleotide-dependent gating of ATP-sensitive K+ (KATP) channels has been demonstrated. However, it is not known whether dinucleotide polyphosphates, a family of endogenous compounds structurally-related to ATP, could also modulate this ion conductance. Therefore, in the present study we assessed the direct effect of diadenosine 5′,5″-P1,P5-pentaphosphate (Ap5A) on cardiac KATP channel activity using the inside-out configuration of the patch-clamp technique. Addition of Ap5A (50 μM) to the internal side of membrane patches, excised from guinea-pig ventricular cells, strongly inhibited KATP channel activity. The estimated NPo (where N is the number of channels in the patch and Po the open probability of each channel) was 4.16 ± 0.50 in the absence and 0.85 ± 0.30 in the presence of Ap5A (50 μM). This effect of Ap5A was partially reversible, and the NP0 was 2.26 ± 0.60 after washout of Ap5A. Exposure of KATP channels to increasing concentrations of Ap5A revealed that the Ap5A-induced inhibition is concentration-dependent with the half-maximal effective concentration of 16 μM (Hill coefficient: 1.6). On the basis of these results, we conclude that Ap5A is a potent antagonist of the KATP channel activity. This represents a previously unrecognized property of Ap5A, as well as the discovery of a potentially novel endogenous ligand of myocardial KATP channels.",
keywords = "ATP-sensitive K channel, Cardiomyocyte, Channel gating, Diadenosine pentaphosphate, Diadenosine polyphosphates, Heart",
author = "Aleksandar Jovanovic and Alekseev, {Alexey E.} and Andre Terzic",
year = "1996",
language = "English (US)",
volume = "353",
pages = "241--244",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Cardiac ATP-sensitive K+ channel

T2 - A target for diadenosine 5′,5″-P1,P5-pentaphosphate

AU - Jovanovic, Aleksandar

AU - Alekseev, Alexey E.

AU - Terzic, Andre

PY - 1996

Y1 - 1996

N2 - In numerous studies the intracellular mononucleotide-dependent gating of ATP-sensitive K+ (KATP) channels has been demonstrated. However, it is not known whether dinucleotide polyphosphates, a family of endogenous compounds structurally-related to ATP, could also modulate this ion conductance. Therefore, in the present study we assessed the direct effect of diadenosine 5′,5″-P1,P5-pentaphosphate (Ap5A) on cardiac KATP channel activity using the inside-out configuration of the patch-clamp technique. Addition of Ap5A (50 μM) to the internal side of membrane patches, excised from guinea-pig ventricular cells, strongly inhibited KATP channel activity. The estimated NPo (where N is the number of channels in the patch and Po the open probability of each channel) was 4.16 ± 0.50 in the absence and 0.85 ± 0.30 in the presence of Ap5A (50 μM). This effect of Ap5A was partially reversible, and the NP0 was 2.26 ± 0.60 after washout of Ap5A. Exposure of KATP channels to increasing concentrations of Ap5A revealed that the Ap5A-induced inhibition is concentration-dependent with the half-maximal effective concentration of 16 μM (Hill coefficient: 1.6). On the basis of these results, we conclude that Ap5A is a potent antagonist of the KATP channel activity. This represents a previously unrecognized property of Ap5A, as well as the discovery of a potentially novel endogenous ligand of myocardial KATP channels.

AB - In numerous studies the intracellular mononucleotide-dependent gating of ATP-sensitive K+ (KATP) channels has been demonstrated. However, it is not known whether dinucleotide polyphosphates, a family of endogenous compounds structurally-related to ATP, could also modulate this ion conductance. Therefore, in the present study we assessed the direct effect of diadenosine 5′,5″-P1,P5-pentaphosphate (Ap5A) on cardiac KATP channel activity using the inside-out configuration of the patch-clamp technique. Addition of Ap5A (50 μM) to the internal side of membrane patches, excised from guinea-pig ventricular cells, strongly inhibited KATP channel activity. The estimated NPo (where N is the number of channels in the patch and Po the open probability of each channel) was 4.16 ± 0.50 in the absence and 0.85 ± 0.30 in the presence of Ap5A (50 μM). This effect of Ap5A was partially reversible, and the NP0 was 2.26 ± 0.60 after washout of Ap5A. Exposure of KATP channels to increasing concentrations of Ap5A revealed that the Ap5A-induced inhibition is concentration-dependent with the half-maximal effective concentration of 16 μM (Hill coefficient: 1.6). On the basis of these results, we conclude that Ap5A is a potent antagonist of the KATP channel activity. This represents a previously unrecognized property of Ap5A, as well as the discovery of a potentially novel endogenous ligand of myocardial KATP channels.

KW - ATP-sensitive K channel

KW - Cardiomyocyte

KW - Channel gating

KW - Diadenosine pentaphosphate

KW - Diadenosine polyphosphates

KW - Heart

UR - http://www.scopus.com/inward/record.url?scp=0030070761&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030070761&partnerID=8YFLogxK

M3 - Article

C2 - 8717166

AN - SCOPUS:0030070761

VL - 353

SP - 241

EP - 244

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 2

ER -