Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis

A. N. Lopatin, Lisa Shantz, C. A. Mackintosh, C. G. Nichols, Anthony Pegg

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Inward rectification of cardiac I(K1) channels was modulated by genetic manipulation of the naturally occurring polyamines. Ornithine decarboxylase (ODC) was overexpressed in mouse heart under control of the cardiac α-myosin heavy chain promoter (αMHC). In ODC transgenic hearts, putrescine and cadaverine levels were highly elevated (~ 35-fold for putrescine), spermidine was increased 3.6-fold, but spermine was essentially unchanged. I(K1) density was reduced by ~ 38%, although the voltage-dependence of rectification was essentially unchanged. Interestingly, the fast component of transient outward (I(to.f)) current was increased, but the total outward current amplitude was unchanged. I(K1) and I(to) currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine. I(K1) current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification. Intracellular dialysis of myocytes with putrescine, spermidine and spermine caused reduction, no change and increase of the steepness of rectification, respectively. Taken together with kinetic analysis of I(K1) activation these results are consistent with spermine being a major rectifying factor at potentials positive to E(K), spermidine dominating at potentials around and negative to E(K), and putrescine playing no significant role in rectification in the mouse heart. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)2007-2024
Number of pages18
JournalJournal of Molecular and Cellular Cardiology
Volume32
Issue number11
DOIs
StatePublished - Jan 1 2000

Fingerprint

Spermine
Potassium Channels
Polyamines
Putrescine
Transgenic Mice
Spermidine
Muscle Cells
Ornithine Decarboxylase
Spermine Synthase
Cadaverine
Cardiac Myosins
Myosin Heavy Chains
Dialysis
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{f8ebcc1790114343953769458636ade5,
title = "Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis",
abstract = "Inward rectification of cardiac I(K1) channels was modulated by genetic manipulation of the naturally occurring polyamines. Ornithine decarboxylase (ODC) was overexpressed in mouse heart under control of the cardiac α-myosin heavy chain promoter (αMHC). In ODC transgenic hearts, putrescine and cadaverine levels were highly elevated (~ 35-fold for putrescine), spermidine was increased 3.6-fold, but spermine was essentially unchanged. I(K1) density was reduced by ~ 38{\%}, although the voltage-dependence of rectification was essentially unchanged. Interestingly, the fast component of transient outward (I(to.f)) current was increased, but the total outward current amplitude was unchanged. I(K1) and I(to) currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine. I(K1) current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification. Intracellular dialysis of myocytes with putrescine, spermidine and spermine caused reduction, no change and increase of the steepness of rectification, respectively. Taken together with kinetic analysis of I(K1) activation these results are consistent with spermine being a major rectifying factor at potentials positive to E(K), spermidine dominating at potentials around and negative to E(K), and putrescine playing no significant role in rectification in the mouse heart. (C) 2000 Academic Press.",
author = "Lopatin, {A. N.} and Lisa Shantz and Mackintosh, {C. A.} and Nichols, {C. G.} and Anthony Pegg",
year = "2000",
month = "1",
day = "1",
doi = "10.1006/jmcc.2000.1232",
language = "English (US)",
volume = "32",
pages = "2007--2024",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "11",

}

Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis. / Lopatin, A. N.; Shantz, Lisa; Mackintosh, C. A.; Nichols, C. G.; Pegg, Anthony.

In: Journal of Molecular and Cellular Cardiology, Vol. 32, No. 11, 01.01.2000, p. 2007-2024.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Modulation of potassium channels in the hearts of transgenic and mutant mice with altered polyamine biosynthesis

AU - Lopatin, A. N.

AU - Shantz, Lisa

AU - Mackintosh, C. A.

AU - Nichols, C. G.

AU - Pegg, Anthony

PY - 2000/1/1

Y1 - 2000/1/1

N2 - Inward rectification of cardiac I(K1) channels was modulated by genetic manipulation of the naturally occurring polyamines. Ornithine decarboxylase (ODC) was overexpressed in mouse heart under control of the cardiac α-myosin heavy chain promoter (αMHC). In ODC transgenic hearts, putrescine and cadaverine levels were highly elevated (~ 35-fold for putrescine), spermidine was increased 3.6-fold, but spermine was essentially unchanged. I(K1) density was reduced by ~ 38%, although the voltage-dependence of rectification was essentially unchanged. Interestingly, the fast component of transient outward (I(to.f)) current was increased, but the total outward current amplitude was unchanged. I(K1) and I(to) currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine. I(K1) current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification. Intracellular dialysis of myocytes with putrescine, spermidine and spermine caused reduction, no change and increase of the steepness of rectification, respectively. Taken together with kinetic analysis of I(K1) activation these results are consistent with spermine being a major rectifying factor at potentials positive to E(K), spermidine dominating at potentials around and negative to E(K), and putrescine playing no significant role in rectification in the mouse heart. (C) 2000 Academic Press.

AB - Inward rectification of cardiac I(K1) channels was modulated by genetic manipulation of the naturally occurring polyamines. Ornithine decarboxylase (ODC) was overexpressed in mouse heart under control of the cardiac α-myosin heavy chain promoter (αMHC). In ODC transgenic hearts, putrescine and cadaverine levels were highly elevated (~ 35-fold for putrescine), spermidine was increased 3.6-fold, but spermine was essentially unchanged. I(K1) density was reduced by ~ 38%, although the voltage-dependence of rectification was essentially unchanged. Interestingly, the fast component of transient outward (I(to.f)) current was increased, but the total outward current amplitude was unchanged. I(K1) and I(to) currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine. I(K1) current densities were not altered in Gy myocytes, but the steepness of rectification was reduced indicating a role for spermine in controlling rectification. Intracellular dialysis of myocytes with putrescine, spermidine and spermine caused reduction, no change and increase of the steepness of rectification, respectively. Taken together with kinetic analysis of I(K1) activation these results are consistent with spermine being a major rectifying factor at potentials positive to E(K), spermidine dominating at potentials around and negative to E(K), and putrescine playing no significant role in rectification in the mouse heart. (C) 2000 Academic Press.

UR - http://www.scopus.com/inward/record.url?scp=0033747576&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033747576&partnerID=8YFLogxK

U2 - 10.1006/jmcc.2000.1232

DO - 10.1006/jmcc.2000.1232

M3 - Article

VL - 32

SP - 2007

EP - 2024

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 11

ER -