Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes

K. Nakayama, Zheng Fan, F. Marumo, M. Hiraoka

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration ([ATP](i)) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP](i). Pinacidil at 5 μM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP](i) from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP](i) showed a shift to the right and a depression of the maximum response at increased [ATP](i). The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 μM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP](i). The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.

Original languageEnglish (US)
Pages (from-to)1124-1133
Number of pages10
JournalCirculation Research
Volume67
Issue number5
DOIs
StatePublished - Jan 1 1990
Externally publishedYes

Fingerprint

Pinacidil
Muscle Cells
Guinea Pigs
Adenosine Triphosphate
Action Potentials
Glyburide
Patch-Clamp Techniques

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes. / Nakayama, K.; Fan, Zheng; Marumo, F.; Hiraoka, M.

In: Circulation Research, Vol. 67, No. 5, 01.01.1990, p. 1124-1133.

Research output: Contribution to journalArticle

@article{3dcc00e7981d44e09ff3942962c94b17,
title = "Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes",
abstract = "The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration ([ATP](i)) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP](i). Pinacidil at 5 μM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP](i) from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP](i) showed a shift to the right and a depression of the maximum response at increased [ATP](i). The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 μM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP](i). The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.",
author = "K. Nakayama and Zheng Fan and F. Marumo and M. Hiraoka",
year = "1990",
month = "1",
day = "1",
doi = "10.1161/01.RES.67.5.1124",
language = "English (US)",
volume = "67",
pages = "1124--1133",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes

AU - Nakayama, K.

AU - Fan, Zheng

AU - Marumo, F.

AU - Hiraoka, M.

PY - 1990/1/1

Y1 - 1990/1/1

N2 - The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration ([ATP](i)) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP](i). Pinacidil at 5 μM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP](i) from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP](i) showed a shift to the right and a depression of the maximum response at increased [ATP](i). The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 μM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP](i). The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.

AB - The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration ([ATP](i)) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP](i). Pinacidil at 5 μM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP](i) from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP](i) showed a shift to the right and a depression of the maximum response at increased [ATP](i). The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 μM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP](i). The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.

UR - http://www.scopus.com/inward/record.url?scp=0025027643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025027643&partnerID=8YFLogxK

U2 - 10.1161/01.RES.67.5.1124

DO - 10.1161/01.RES.67.5.1124

M3 - Article

VL - 67

SP - 1124

EP - 1133

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 5

ER -