title: Abnormal function of platelet G proteins in long QT syndrome.
abstract: Several hypotheses have been proposed for the pathophysiology of the congenital long QT syndrome, however, the underlying mechanism has not yet been elucidated. This study evaluated G protein function in patients with congenital long QT syndrome (LQTS) and compared it with that of normal subjects. Platelet-rich plasma was collected and the cyclic AMP (cAMP) level of platelets was measured in three conditions utilizing radioimmunoassay: the basal state (Basal cAMP), after stimulation by PGE1 (PGE1-cAMP), and after stimulation by PGE1 followed by inhibition by adrenaline (Adr-cAMP), and the results were compared between 7 LQTS patients and 10 healthy volunteers (control). Gs function was defined as (PGE1-cAMP)/(Basal cAMP) and Gi function as ¿(PGE1-cAMP)-(Adr-cAMP)¿/(PGE1-cAMP). Basal cAMP was lower in patients than in the controls: 2.9 +/- 0.6 pmol/ 10(8) cells vs. 4.2 +/- 0.7 pmol/10(8) cells (p < 0.05). The increase in cAMP after PGE1 was similar in the two groups but the peak was lower in the patients: 16.8 +/- 6.2 pmol/10(8) cells vs. 24.8 +/- 7.4 pmol/10(8) cells (PGE1-cAMP). After addition of adrenaline, cAMP decreased to 14.2 +/- 5.8 pmol/10(8) cells vs. 16.2 +/- 7.6 pmol/10(8) cells and the change was significantly smaller in the patients than in the controls: 0.17 +/- 0.12 vs. 0.38 +/- 0.16 (p < 0.05). Basal cAMP was weakly correlated with sinus cycle length (r = -0.48, p > 0.3) and QTc was correlated with Gs function (r = 0.52, p > 0.3) but not with Gi function. Patients with associated Torsade de Pointes had a significantly lower Gi function compared to those without (p < 0.05). In LQTS patients, G protein function was abnormal and the abnormality was associated with clinical characteristics of long QT syndrome. The relationship between the abnormal G protein function and the regulation of the repolarization of the ventricular myocardium needs to be studied further.
authors.affiliation: First Department of Internal Medicine, Niigata University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Washizuka
authors.forename: Y
authors.initials: Y
authors.lastname: Aizawa
authors.forename: I
authors.initials: I
authors.lastname: Fuse
authors.forename: A
authors.initials: A
authors.lastname: Shibata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry*; D000242:Cyclic AMP / Q000097:blood; D004562:Electrocardiography; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D008133:Long QT Syndrome / Q000097:blood* / Q000151:congenital / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016171:Torsades de Pointes / Q000097:blood
chemical_list: D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D000527:Alprostadil; D004837:Epinephrine