title: Expression of Kir2.1 and Kir6.2 transgenes under the control of the alpha-MHC promoter in the sinoatrial and atrioventricular nodes in transgenic mice.
abstract: Kir2.1 and Kir6.2 are ion channel subunits partly responsible for the background inward rectifier and ATP-sensitive K(+) currents (I(K1) and I(KATP)) in the heart. Very little is known about how the distribution of ion channel subunits is controlled. In this study, we have investigated the expression (at protein and mRNA levels) of GFP-tagged Kir2.1 and Kir6.2 transgenes under the control of the alpha-MHC promoter in the sinoatrial node (SAN), atrioventricular node (AVN), His bundle and working myocardium of transgenic mice. After dissection, serial 10-microm cryosections were cut. Histological staining was carried out to identify tissues, confocal microscopy was carried out to map the distribution of the GFP-tagged ion channel subunits and in situ hybridization was carried out to map the distribution of corresponding mRNAs. We demonstrate heterologous expression of the ion channel subunits in the working myocardium, but not necessarily in the SAN, AVN or His bundle; the distribution of the subunits does not correspond to the expected distribution of alpha-MHC. Both protein and mRNA expression does, however, correspond to the expected distributions of native Kir6.2 and Kir2.1 in the SAN, AVN, His bundle and working myocardium. The data demonstrate novel transcriptional and/or post-transcriptional control of ion channel subunit expression and raise important questions about the control of regional expression of ion channels.
authors.affiliation: Cardiovascular Research Group, School of Medicine, University of Manchester, Core Technology Facility, 46 Grafton Street, Manchester M13 9NT, UK. halina.dobrzynski@manchester.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Dobrzynski
authors.forename: R
authors.initials: R
authors.lastname: Billeter
authors.forename: I D
authors.initials: ID
authors.lastname: Greener
authors.forename: J O
authors.initials: JO
authors.lastname: Tellez
authors.forename: N J
authors.initials: NJ
authors.lastname: Chandler
authors.forename: T P
authors.initials: TP
authors.lastname: Flagg
authors.forename: C G
authors.initials: CG
authors.lastname: Nichols
authors.forename: A N
authors.initials: AN
authors.lastname: Lopatin
authors.forename: M R
authors.initials: MR
authors.lastname: Boyett
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000378:metabolism*; D001683:Biological Clocks; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012849:Sinoatrial Node / Q000378:metabolism*; D019076:Transgenes; D000099161:Kcnj11 Channel
chemical_list: D018995:Myosin Heavy Chains; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C489461:Kir2.1 channel