T-type Ca2+ channels are involved in high glucose-induced rat neonatal cardiomyocyte proliferation.
Infants develop hypertrophic cardiomyopathy in approximately 30% of diabetic pregnancies. We have characterized the effects of glucose on voltage-gated T-type Ca2+ channels and intracellular free calcium concentration, [Ca2+]i in neonatal rat cardiomyocytes. We found that T-type Ca2+ channel current density increased significantly in primary culture neonatal cardiac myocytes that were treated with 25 mM glucose for 48 h when compared with those that were treated with 5 mM glucose. High-glucose treatment also caused a higher Ca2+ influx elicited by 50 mM KCl in the myocytes. KCl-induced Ca2+ influx was attenuated when nickel was present. Real-time PCR studies demonstrated that mRNA levels of both alpha1G (Ca(v)3.1) and alpha1H (Ca(v)3.2) T-type Ca2+ channels were elevated after high-glucose treatment. High-glucose also significantly increased ventricular cell proliferation as well as the proportion of cells in the S-phase of the cell cycle; both effects were reversed by nickel or mibefradil. These results indicate that high glucose causes a rise in [Ca2+]i in neonatal cardiac myocytes by a mechanism that is associated with the regulation of the T-type Ca2+ channel activity.
Li
Ming
M
Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA. mli@tulane.edu
Zhang
Min
M
Huang
Luping
L
Zhou
Jianxin
J
Zhuang
Hean
H
Taylor
James T
JT
Keyser
Brian M
BM
Whitehurst
Richard M
RM
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats
D020747:Calcium Channels, T-Type; D002712:Chlorides; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; D021122:Protein Subunits; D005947:Glucose; D002118:Calcium