Molecular Organization of the Terminal Domains of the TRPV1 Ion Channel Determined by FRET Spectroscopy

Abstract

mortality than at 2 months or later. At 2 months they often die suddenly without clear symptoms of HF, whereas at 3 months, many of them showed evident symptoms of HF. In isolated left ventricular myocardium (LV) from 2 month-mice, spontaneous activity frequently occurred and action potential duration was prolonged. Transient outward (I to) and ultrarapid delayed rectifier K þ currents (I Kur) were significantly reduced in DCM myocytes. Correspondingly, down-regulation of Kv4.2, Kv1.5 and KChIP2 was evident in mRNA and protein levels. In 3 month-LV, more frequent spontaneous activity and further down-regulation in above K þ channels were observed. 1 month mice, on the contrary, showed infrequent spontaneous activity in LV, in which Kv4.2 but not Kv1.5 or KChIP2 was down-regulated. Because they are at low risk of death in spite of enlarged hearts, reduction in Kv4.2 is not sufficient for sudden death (SD). Our results suggest that the combined down-regulation of Kv4.2, Kv1.5 and KChIP2 prior to the onset of HF may play an important role in the premature SD in this DCM model.