Reduction in ~(125)I-Dofetilide B_(max) and elevation of verapamil in L-thyroxin induced hypertrophied guinea pig ventricular membrane / 中国药理学通报

ABSTRACT

AIM To determine whether the I Kr channel protein is altered and its response to dofetilide and verapamil in cardiac remodeling by L thy roxin. METHODS Saturation binding assays in guinea pig ventricular membrane preparation with 125 I dofetilide, a radioligand for the cardiac rapidly activating delayed outward rectifier channel (I Kr ) was conducted respectively in normal, hypertrophied, Verapamil or dofetilide intervened group. RESULTS Scatchard analysis revealed two binding sites with different affinities in normal guinea pig ventricle a high affinity site [ K d=(1 27?0 11) nmol, B max =(34 67?3 23) nmol?g -1 ] and a low affinity site [ K d=(43 48?4 83) nmol, B max =(76 41?5 37) nmol?g -1 ] ( n =5), only the high affinity site was associated with the I Kr in guinea pig ventricle. The B max of high affinity site in the hypertrophied ventricle induced by L thyroxin was down regulated to (18 13?2 27) nmol?g -1 ( n =6). Verapamil was effective to up regulate the high affinity B max to (37 26?4 32) nmol?g -1 ( n =5) but dofetilide had hardly effect on it. CONCLUSION The I Kr channel protein in guinea pig ventricular membrane was down regulated in remodeling ventricle by chronic L thyroxin treatment and improved by verapamil.