title: Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit.
abstract: 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(+), Ca(2+), hyperpolarization-activated cation and K(+) channels, and related Ca(2+) 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.
authors.affiliation: University of Manchester, Manchester, M13 9NT, UK.
authors.forename: James O
authors.initials: JO
authors.lastname: Tellez
authors.forename: Halina
authors.initials: H
authors.lastname: Dobrzynski
authors.forename: Ian D
authors.initials: ID
authors.lastname: Greener
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Graham
authors.forename: Emma
authors.initials: E
authors.lastname: Laing
authors.forename: Haruo
authors.initials: H
authors.lastname: Honjo
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Hubbard
authors.forename: Mark R
authors.initials: MR
authors.lastname: Boyett
authors.forename: Rudi
authors.initials: R
authors.lastname: Billeter
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D017630:Connexins / Q000235:genetics; D054815:Cyclic Nucleotide-Gated Cation Channels; D005786:Gene Expression Regulation; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D015221:Potassium Channels / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D011817:Rabbits; D012849:Sinoatrial Node / Q000502:physiology*; D015222:Sodium Channels / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
chemical_list: D015220:Calcium Channels; D017630:Connexins; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D012333:RNA, Messenger; D012339:RNA, Ribosomal, 28S; D015222:Sodium Channels; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000254:Sodium-Potassium-Exchanging ATPase