Impaired cardiac excitation-contraction coupling in ventricular myocytes from Ames dwarf mice with IGF-I deficiency.
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are involved in the regulation of cardiovascular function. GH/IGF-I deficiency is associated with impaired cardiac performance manifested as reduced left ventricular ejection fraction and diastolic filling. This study was to determine the impact of IGF-I deficiency on single cardiac myocyte excitation-contraction (E-C) coupling. Ventricular myocytes were isolated from adult Ames dwarf mice and age-matched wild-type siblings. Dwarf mice are characterized by severe IGF-I deficiency. Mechanical properties were evaluated using a video edge detection system. Myocytes were electrically stimulated at 0.5 Hz. The contractile properties analysed included peak shortening (PS), time to peak shortening (TPS) and time to 90% relengthening (TR(90)), and maximal velocities of shortening/relengthening (+/-d L/d t). Intracellular Ca(2+) transients were evaluated by fura-2 fluorescence microscopy. Dwarf mice exhibited significantly reduced body and heart weights and severely deficient plasma IGF-I. Myocytes from dwarf mice displayed significantly smaller cell lengths (CLs), prolonged TPS/TR(90) and reduced +/-d L/d t compared with the wild-type littermates. The absolute PS was similar although PS/CL was enhanced in the dwarf group. Myocytes from dwarf animals displayed reduced peak intracellular Ca(2+) levels and slowed intracellular Ca(2+) clearing associated with a comparable resting intracellular Ca(2+). Furthermore, myocytes from the dwarf hearts were equally responsive to an elevation in extracellular Ca(2+) and exhibited an augmented stepwise decrease in response to minimal increase in stimulating frequencies compared with those from the wild-type group. These results suggest that deficiency in IGF-I may be directly associated with cardiac E-C coupling dysfunction at the ventricular myocyte level.
Ren
Jun
J
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks 58203, USA. jren@medicine.nodak.edu
Brown-Borg
Holly M
HM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology*; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D002118:Calcium