Cardiac electrophysiologic effects of parathyroid hormone in the guinea pig.
The cardiac electrophysiologic effects of parathyroid hormone (PTH) were studied in three different experimental models. Purified synthetic human parathyroid hormone (hPTH 1-84), at a dose of 30 ng/g body weight (BW), prolonged the QT interval of surface ECGs in intact guinea pigs. To further clarify the mechanisms of the QT prolongation caused by hPTH, the action potentials of guinea pig papillary muscle were recorded by conventional microelectrode techniques. hPTH (10(-7)M) prolonged the action potential duration without changing the action potential amplitude, resting potential, maximal upstroke velocity of the action potential, or maximal repolarization rate. hPTH affected only the plateau phase, in a concentration-dependent fashion. The half-maximum concentration was 6.8 x 10(-8)M for action potential duration at 30% repolarization (APD30), 3.2 x 10(-8)M for APD50, and 2.1 x 10(-8)M for APD90. In isolated single guinea pig ventricular cells, the patch clamp method was used to record the slow inward calcium current (ICa) and delayed rectifier potassium current (IK) responsible for the action potential plateau phase. hPTH increased the peak amplitude of ICa at + 10mV by an average of 42%, and increased IK at + 10mV by 85%. These results indicate that, in ventricular muscle, hPTH prolongs the action potential duration and QT interval by the balance of the prolongation effect on APD by enhancing the slow inward calcium current and the shortening effect on APD by enhancing the delayed rectifier potassium current.
Ebisawa
K
K
Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Kimura
K
K
Nakayama
T
T
Yaginuma
T
T
Watanabe
Y
Y
Shimada
K
K
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology
D010281:Parathyroid Hormone; D011188:Potassium; D002118:Calcium