Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit

被引:129
作者
Tellez, James O.
Dobrzynski, Halina
Greener, Ian D.
Graham, Gillian M.
Laing, Emma
Honjo, Haruo
Hubbard, Simon J.
Boyett, Mark R.
Billeter, Rudi
机构
[1] Univ Manchester, Cardiovasc Res Grp, Core Technol Facil, Manchester M13 9NT, Lancs, England
[2] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England
[3] Nagoya Univ, Nagoya, Aichi, Japan
[4] Univ Nottingham, Nottingham NG7 2RD, England
关键词
sinoatrial node; pacemaker; Na+ channels; Ca2(+) channels; HCN channels; K+ channels;
D O I
10.1161/01.RES.0000251717.98379.69
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The aim of the study was to identify ion channel transcripts expressed in the sinoatrial node (SAN), the pacemaker of the heart. Functionally, the SAN can be divided into central and peripheral regions (center is adapted for pacemaking only, whereas periphery is adapted to protect center and drive atrial muscle as well as pacemaking) and the aim was to study expression in both regions. In rabbit tissue, the abundance of 30 transcripts (including transcripts for connexin, Na+, Ca2+, hyperpolarization-activated cation and K+ channels, and related Ca2+ handling proteins) was measured using quantitative PCR and the distribution of selected transcripts was visualized using in situ hybridization. Quantification of individual transcripts (quantitative PCR) showed that there are significant differences in the abundance of 63% of the transcripts studied between the SAN and atrial muscle, and cluster analysis showed that the transcript profile of the SAN is significantly different from that of atrial muscle. There are apparent isoform switches on moving from atrial muscle to the SAN center: RYR2 to RYR3, Na(v)1.5 to Na(v)1.1, Ca(v)1.2 to Ca(v)1.3 and K(v)1.4 to K(v)4.2. The transcript profile of the SAN periphery is intermediate between that of the SAN center and atrial muscle. For example, Na(v)1.5 messenger RNA is expressed in the SAN periphery (as it is in atrial muscle), but not in the SAN center, and this is probably related to the need of the SAN periphery to drive the surrounding atrial muscle.
引用
收藏
页码:1384 / 1393
页数:10
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