Expression of hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN4) is increased in hypertrophic cardiomyopathy.
OBJECTIVE
Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium with uncertain etiology and often leads to sudden death as the result of arrhythmia. Pacemaker hyperpolarization-activated current I(f) was altered in hypertrophic hearts and was probably responsible for arrhythmia. I(f) channels are compose\d of four hyperpolarization-activated cyclic nucleotide-gated cation subunits (HCN1-4). A previous study found significantly high levels of HCN2 and HCN4 mRNA in hypertrophic hearts compared to control hearts in septum and left ventricles in rats. No studies, however, have investigated the HCN gene expression in the myocardium from human HCM heart.


METHODS
The left ventricular tissue from four patients who died of HCM and six healthy patients who died of motor vehicle accidents was included in this study. The fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect HCN4 mRNA. The expression of HCN4 mRNA of the two groups was detected on the assay.


RESULTS
In the HCM hearts, disorganization of the hypertrophic myofibers and interstitial fibrosis were observed in all four patients, although absent in healthy control hearts. By quantitative polymerase chain reaction, the mean copy number of HCN4 mRNA was 2.2×10(7) (range, 6.8×10(6) to 4.55×10(7)) in HCM hearts and 8.17×10(3) (range, 8.76×10(1) to 3.5×10(4)) in control hearts (P=.0318).


CONCLUSIONS
Higher HCN4 mRNA levels in the HCM hearts suggest that up-regulation of HCN4 gene expression might be responsible for ventricular arrhythmia that leads to sudden death.
Wei-qing
Huang
H
Department of Pathology, Qingdao Municipal Hospital, Qingdao 266071, Shandong, China.
Qing-nuan
Kong
K
Lin
Xu
X
Cheng-hao
Guo
G
Qi-yi
Zhang
Z
D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D054815:Cyclic Nucleotide-Gated Cation Channels; C119587:HCN4 protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009124:Muscle Proteins; D015221:Potassium Channels; D012333:RNA, Messenger