Age-related down-regulation of HCN channels in rat sinoatrial node.

Aging is associated with deteriorated sinoatrial (SA) node function. The pacemaker current (If) carried by hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels plays a key role in the generation of spontaneous activity of the SA node cells. In the present study, the SA node cells were identified and isolated using the laser capture microdissection (LCM) technique for quantitative analysis of the HCN channel isoforms HCN1-HCN4 transcripts. Using real-time quantitative reverse transcription- polymerase chain reaction (RT-PCR), marked down-regulated transcriptions of HCN2 and HCN4 were observed in the SA node from young (1-month-old) to adult (4-month-old) and further to aged (30- month-old) rats. However, neither the HCN1 nor HCN3 transcript was detectable throughout the lifespan of the rat. Consistently, the effect of 2 mM Cs+ to selectively block the HCN channels, on pacemaking was also lessened with age. Our findings raise the possibility that the down-regulated transcription and relative function of HCN channels may contribute to the decline of the SA node function in aged rats.