Enrichment of G protein alpha-subunit mRNAS in the AV-conducting system of the mammalian heart.
We investigated the expression pattern of the heterotrimeric G proteins Gs alpha, Gi alpha-2 and Go alpha in rat and guinea-pig heart by in situ hybridization. Cryosections were hybridized with single-stranded 35S-cRNA probes complementary to subtype-specific sequences of the respective mRNAs. Hybridization signals were visualized by exposition to X-ray films and dipping autoradiography. The rank order of abundance was Gi alpha-2 approximately Gs alpha >> Go alpha. In general, G protein alpha-subunit mRNAs were evenly distributed in the heart including endo- and epicardium, large vessels and valves. Go alpha-mRNA levels were significantly higher in atria than in ventricles. In contrast to the rather uniform labeling of working myocardium, expression of all three G proteins was enriched in small intramural blood vessels and in subendocardial Purkinje fibers of septum and papillary muscles. A more marked enrichment of Gs alpha-, Gi alpha-2- and especially Go alpha-mRNA was seen in neuronal ganglionic cells in the atrial septum and posterior regions of the atrium. The main finding, however, was an enrichment of all three G protein mRNAs in the atrioventricular conductive tissue. The accumulation was strictly co-localized with acetylcholinesterase-positive regions identified as the atrioventricular node, the bundle of His and the right and left bundle branches and was seen similarly in rat and guinea-pig hearts. Quantitative in situ hybridization revealed Gs alpha-, Gi alpha-2- and Go alpha-mRNA levels in the bundle of His to be 206 +/- 0.13%. 191 +/- 0.15% and 165 +/- 0.06%, respectively, of that in the surrounding interventricular working myocardium. These findings indicate that heterotrimeric G proteins play an important role in modulation of electrical conductance in the heart.
Eschenhagen
T
T
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus, Hamburg, Germany.
Laufs
U
U
Schmitz
W
W
Scholz
H
H
Warnholtz
A
A
Weil
J
J
Schäfer
H J
HJ
D000110:Acetylcholinesterase / Q000032:analysis; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001283:Atrioventricular Node / Q000378:metabolism*; D001923:Brain Chemistry; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D006168:Guinea Pigs; D006346:Heart Septum / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000110:Acetylcholinesterase; D019204:GTP-Binding Proteins