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, L. M.
AU - Mackintosh, C. A.
AU - Nichols, C. G.
AU - Pegg, A. E.
N1 - Funding Information:
This work was primarily supported by a Scientist Development Grant from the American Heart Association (ANL), an Established Investigator grant from the American Heart Association (LMS) and also by grants from the NIH (GM57892 to ANL, HL54171 to CGN, CA18138 and GM26290 to AEP). We thank Dr R. A. Meyer, Jr of the Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte for his generous gift of Gy mice, and Ms Rebecca Dunlap for technical assistance.
PY - 2000
Y1 - 2000
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.
KW - K currents
KW - Ornithine decarboxylase
KW - Polyamines
KW - Rectification
UR - http://www.scopus.com/inward/record.url?scp=0033747576&partnerID=8YFLogxK
U2 - 10.1006/jmcc.2000.1232
DO - 10.1006/jmcc.2000.1232
M3 - Article
C2 - 11040105
AN - SCOPUS:0033747576
SN - 0022-2828
VL - 32
SP - 2007
EP - 2024
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 11
ER -