IGF-I regulates K(+)-channel expression of cultured neonatal rat ventricular myocytes.
Insulin-like growth factor (IGF) I has been known as an important peptide during heart development and myocardial hypertrophy. In the present study, the effects of IGF-I on cardiac K(+)-channel expression were investigated in cultured neonatal rat ventricular myocytes. Two distinct 4-aminopyridine (AP)-sensitive and rapidly activating outward K+ currents (IK) were observed. The predominant K(+)-channel current in cultured cells was a fast inactivating current similar to a 4-AP-sensitive transient outward current [I(to) half-maximal inhibitory concentration (IC60) = 0.87 mM]. Some cells lacking I(to) expressed an IK with little or no slow inactivation. IK exhibited higher sensitivity to inhibition by 4-AP (IC50 = 66.5 microM) and could be enhanced by isoproterenol but unaffected by tetraethylammonium. These characteristics indicate that IK might be the rat isoform of ultrarapid delayed rectifier K+ current IKur previously described in human atrial myocytes. Seventy-two-hour exposure to 60 ng/ml IGF-I induced myocyte hypertrophy and increased the percentage of cells expressing only IKur and the cells expressing both Ito and IKur. In some cultured myocytes, immunofluorescent staining with a polyclonal antibody specific to the COOH terminus of Kv1.5 K(+)-channel protein was performed in the same single cells after voltage-clamp recordings. The IGF-I-pretreated cells expressing larger IKur revealed a significantly intense antibody labeling. These observations indicate that the long-term administration of IGF-I can regulate the K(+)-channel expression of cultured neonatal rat ventricular myocytes. This is important for understanding the role of IGF-I in the modulation of cardiac excitability.
Guo
W
W
Department of Circulation, Nagoya University, Japan.
Kada
K
K
Kamiya
K
K
Toyama
J
J
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002478:Cells, Cultured; D004594:Electrophysiology; D019084:Fluorescent Antibody Technique, Indirect; D006352:Heart Ventricles; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D015221:Potassium Channels; D007334:Insulin-Like Growth Factor I; D015761:4-Aminopyridine