(Circulation. 1998;98:2422-2428.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Differential Distribution of Inward Rectifier Potassium Channel Transcripts in Human Atrium Versus Ventricle
From the Department of Medicine and Research Center, Montreal Heart Institute and University of Montreal, Montreal, Quebec (Z.W., M.W., G.P., S.N.), and the Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec (L.Y., S.N.), Canada.
Correspondence to Dr Zhiguo Wang, Research Center, Montreal Heart Institute, 5000 Bélanger St E, Montreal, Quebec, Canada H1T 1C8. E-mail wangz{at}icm.umontreal.ca
Background—The inward rectifier K+ current (IK1) plays an important role in governing cardiac electrical activity and is well known to have different properties in the atrium compared with the ventricle. Several inward rectifier K+ channel (IRK) subunits (hIRK, HH-IRK1, HIR, and TWIK-1) with different properties have been cloned from human tissues, but their relative expression in cardiac tissues has not been quantified. The present study was designed to define the relative levels of mRNA for various IRKs in human atrium and in failing and nonfailing ventricle.
Methods and Results—Competitive reverse transcription–polymerase chain reaction was used to quantify in human atrium and ventricle the mRNA levels of hIRK, HH-IRK1, HIR, and TWIK-1. The absence of important noncardiac contamination was confirmed by demonstrating a lack of detectable mRNA markers for neuronal (acetylcholine receptor) and vascular (maxi-K channel) tissue. mRNA of HIR was more abundant in normal atrium (7.1±1.3 amol/µg total RNA) than ventricle (0.6±0.1 amol/µg, P<0.05), whereas TWIK-1 mRNA was more concentrated in ventricle (18.1±4.3 amol/µg) than atrium (1.4±0.3 amol/µg, P<0.05). Concentrations of hIRK (42.7±6.7 amol/µg in atrium vs 57.1±9.2 amol/µg in ventricle) and HH-IRK1 (2.0±0.5 amol/µg in atrium vs 1.5±0.5 amol/µg in ventricle) were comparable. No significant differences in IRK subunit transcript concentrations were found between normal and failing ventricles.
Conclusions—mRNAs for all 4 IRKs are detected in human atrium and ventricle, but the mRNA copy number of a low-conductance subunit (HIR) is larger in atrium and the copy number of a weakly rectifying subunit (TWIK-1) is larger in ventricle. These differences in relative message levels may provide a potential molecular basis for different properties of IK1 in human atrium compared with ventricle.
Key Words: atrium • ventricles • heart failure • potassium • RNA
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|
|
|
|
|
|
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