Decreased transient outward K+ current in ventricular myocytes from acromegalic rats.
Cardiac hypertrophy and heart failure are common to acromegalic patients who have abnormally high serum growth hormone (GH). While the function of cardiac muscle is clearly affected by chronically elevated GH, the electrical activity of myocytes from hearts with GH-dependent hypertrophy has not been studied. We used adult, female Wistar-Furth rats with induced GH-secreting tumors to study the effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors were induced by subcutaneous inoculation of GH3 cells. Eight weeks after inoculation, the rats had doubled their body weight and heart size compared with age-matched controls. There were no differences in either action potential amplitude or resting potential of right ventricular myocytes from control and tumor-bearing rats. However, action potential duration increased significantly in tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10) compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action potential was mainly due to a decrease in density of a transient outward current (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/- 0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing rats. The decrease in It,o) and increase in heart weight occurred with a similar time course. The increased action potential duration prolongs Ca2+ influx through L-type Ca2+ channels in the tumor-bearing animals; this may be important in cardiovascular adaptation.
Xu
X P
XP
Department of Physiology and Biophysics, University of Illinois, Urbana-Champaign 61801.
Best
P M
PM
D000172:Acromegaly / Q000503:physiopathology*; D000200:Action Potentials; D000818:Animals; D004594:Electrophysiology; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles; D006706:Homeostasis; D009206:Myocardium / Q000473:pathology; D009368:Neoplasm Transplantation; D011188:Potassium / Q000502:physiology*; D051381:Rats; D011930:Reaction Time; D014407:Tumor Cells, Cultured / Q000378:metabolism
D013006:Growth Hormone; D011188:Potassium