Effects of the renin-angiotensin system on the current I(to) in epicardial and endocardial ventricular myocytes from the canine heart

Hangang Yu, Junyuan Gao, Hongsheng Wang, Randy Wymore, Susan Steinberg, David McKinnon, Michael R. Rosen, Ira S. Cohen

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The Ca 2+ -independent portion of transient outward K + current (I(to)) exhibits a transmural gradient in ventricle. To investigate control mechanisms for this gradient, we studied canine epicardial and endocardial ventricular myocytes with use of the whole-cell patch-clamp technique. I(to) was larger in amplitude, had a more negative voltage threshold for activation, and had a more negative midpoint of inactivation in epicardium. Recovery from inactivation was > 10-fold slower in endocardium. Incubation of epicardial myocytes with angiotensin II for 2 to 52 hours altered I(to) to resemble unincubated endocardium and reduced the amplitude of the phase 1 notch of the action potential. In contrast, incubation of endocardial myocytes with losartan for 2 to 52 hours altered I(to) to resemble unincubated epicardium and induced a phase 1 notch in the action potential. With RNase protection assays, we determined that incubations with angiotensin II or losartan did not alter mRNA levels for either Kv4.3 or Kv1.4; thus, a change in the α subunit for I(to) is unlikely to be responsible. To test whether posttranslational modification produced the effects of angiotensin II, we coexpressed Kv4.3 and the angiotensin II type la receptor in Xenopus oocytes. Incubation with angiotensin II increased the time constant for recovery from inactivation of the expressed current by 2-fold with an incubation time constant of 3.7 hours. No effect on activation or inactivation voltage dependence was observed. These results demonstrate that the properties of I(to) in endocardium and epicardium are plastic and likely under the tonic-differing influence of the renin-angiotensin system.

Original languageEnglish
Pages (from-to)1062-1068
Number of pages7
JournalCirculation Research
Volume86
Issue number10
DOIs
StatePublished - 26 May 2000

Fingerprint

Renin-Angiotensin System
Endocardium
Angiotensin II
Muscle Cells
Canidae
Pericardium
Losartan
Action Potentials
Angiotensin Receptors
Patch-Clamp Techniques
Post Translational Protein Processing
Ribonucleases
Xenopus
Plastics
Oocytes
Messenger RNA

Keywords

  • Angiotensin
  • Current
  • Endocardium
  • Epicardium

Cite this

Yu, Hangang ; Gao, Junyuan ; Wang, Hongsheng ; Wymore, Randy ; Steinberg, Susan ; McKinnon, David ; Rosen, Michael R. ; Cohen, Ira S. / Effects of the renin-angiotensin system on the current I(to) in epicardial and endocardial ventricular myocytes from the canine heart. In: Circulation Research. 2000 ; Vol. 86, No. 10. pp. 1062-1068.
@article{8cc0202c6d3c4968ac001b9c66a6b523,
title = "Effects of the renin-angiotensin system on the current I(to) in epicardial and endocardial ventricular myocytes from the canine heart",
abstract = "The Ca 2+ -independent portion of transient outward K + current (I(to)) exhibits a transmural gradient in ventricle. To investigate control mechanisms for this gradient, we studied canine epicardial and endocardial ventricular myocytes with use of the whole-cell patch-clamp technique. I(to) was larger in amplitude, had a more negative voltage threshold for activation, and had a more negative midpoint of inactivation in epicardium. Recovery from inactivation was > 10-fold slower in endocardium. Incubation of epicardial myocytes with angiotensin II for 2 to 52 hours altered I(to) to resemble unincubated endocardium and reduced the amplitude of the phase 1 notch of the action potential. In contrast, incubation of endocardial myocytes with losartan for 2 to 52 hours altered I(to) to resemble unincubated epicardium and induced a phase 1 notch in the action potential. With RNase protection assays, we determined that incubations with angiotensin II or losartan did not alter mRNA levels for either Kv4.3 or Kv1.4; thus, a change in the α subunit for I(to) is unlikely to be responsible. To test whether posttranslational modification produced the effects of angiotensin II, we coexpressed Kv4.3 and the angiotensin II type la receptor in Xenopus oocytes. Incubation with angiotensin II increased the time constant for recovery from inactivation of the expressed current by 2-fold with an incubation time constant of 3.7 hours. No effect on activation or inactivation voltage dependence was observed. These results demonstrate that the properties of I(to) in endocardium and epicardium are plastic and likely under the tonic-differing influence of the renin-angiotensin system.",
keywords = "Angiotensin, Current, Endocardium, Epicardium",
author = "Hangang Yu and Junyuan Gao and Hongsheng Wang and Randy Wymore and Susan Steinberg and David McKinnon and Rosen, {Michael R.} and Cohen, {Ira S.}",
year = "2000",
month = "5",
day = "26",
doi = "10.1161/01.RES.86.10.1062",
language = "English",
volume = "86",
pages = "1062--1068",
journal = "Circulation research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "10",

}

Effects of the renin-angiotensin system on the current I(to) in epicardial and endocardial ventricular myocytes from the canine heart. / Yu, Hangang; Gao, Junyuan; Wang, Hongsheng; Wymore, Randy; Steinberg, Susan; McKinnon, David; Rosen, Michael R.; Cohen, Ira S.

In: Circulation Research, Vol. 86, No. 10, 26.05.2000, p. 1062-1068.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of the renin-angiotensin system on the current I(to) in epicardial and endocardial ventricular myocytes from the canine heart

AU - Yu, Hangang

AU - Gao, Junyuan

AU - Wang, Hongsheng

AU - Wymore, Randy

AU - Steinberg, Susan

AU - McKinnon, David

AU - Rosen, Michael R.

AU - Cohen, Ira S.

PY - 2000/5/26

Y1 - 2000/5/26

N2 - The Ca 2+ -independent portion of transient outward K + current (I(to)) exhibits a transmural gradient in ventricle. To investigate control mechanisms for this gradient, we studied canine epicardial and endocardial ventricular myocytes with use of the whole-cell patch-clamp technique. I(to) was larger in amplitude, had a more negative voltage threshold for activation, and had a more negative midpoint of inactivation in epicardium. Recovery from inactivation was > 10-fold slower in endocardium. Incubation of epicardial myocytes with angiotensin II for 2 to 52 hours altered I(to) to resemble unincubated endocardium and reduced the amplitude of the phase 1 notch of the action potential. In contrast, incubation of endocardial myocytes with losartan for 2 to 52 hours altered I(to) to resemble unincubated epicardium and induced a phase 1 notch in the action potential. With RNase protection assays, we determined that incubations with angiotensin II or losartan did not alter mRNA levels for either Kv4.3 or Kv1.4; thus, a change in the α subunit for I(to) is unlikely to be responsible. To test whether posttranslational modification produced the effects of angiotensin II, we coexpressed Kv4.3 and the angiotensin II type la receptor in Xenopus oocytes. Incubation with angiotensin II increased the time constant for recovery from inactivation of the expressed current by 2-fold with an incubation time constant of 3.7 hours. No effect on activation or inactivation voltage dependence was observed. These results demonstrate that the properties of I(to) in endocardium and epicardium are plastic and likely under the tonic-differing influence of the renin-angiotensin system.

AB - The Ca 2+ -independent portion of transient outward K + current (I(to)) exhibits a transmural gradient in ventricle. To investigate control mechanisms for this gradient, we studied canine epicardial and endocardial ventricular myocytes with use of the whole-cell patch-clamp technique. I(to) was larger in amplitude, had a more negative voltage threshold for activation, and had a more negative midpoint of inactivation in epicardium. Recovery from inactivation was > 10-fold slower in endocardium. Incubation of epicardial myocytes with angiotensin II for 2 to 52 hours altered I(to) to resemble unincubated endocardium and reduced the amplitude of the phase 1 notch of the action potential. In contrast, incubation of endocardial myocytes with losartan for 2 to 52 hours altered I(to) to resemble unincubated epicardium and induced a phase 1 notch in the action potential. With RNase protection assays, we determined that incubations with angiotensin II or losartan did not alter mRNA levels for either Kv4.3 or Kv1.4; thus, a change in the α subunit for I(to) is unlikely to be responsible. To test whether posttranslational modification produced the effects of angiotensin II, we coexpressed Kv4.3 and the angiotensin II type la receptor in Xenopus oocytes. Incubation with angiotensin II increased the time constant for recovery from inactivation of the expressed current by 2-fold with an incubation time constant of 3.7 hours. No effect on activation or inactivation voltage dependence was observed. These results demonstrate that the properties of I(to) in endocardium and epicardium are plastic and likely under the tonic-differing influence of the renin-angiotensin system.

KW - Angiotensin

KW - Current

KW - Endocardium

KW - Epicardium

UR - http://www.scopus.com/inward/record.url?scp=0034717293&partnerID=8YFLogxK

U2 - 10.1161/01.RES.86.10.1062

DO - 10.1161/01.RES.86.10.1062

M3 - Article

C2 - 10827136

AN - SCOPUS:0034717293

VL - 86

SP - 1062

EP - 1068

JO - Circulation research

JF - Circulation research

SN - 0009-7330

IS - 10

ER -