SummaryPlatelet fibrinogen receptor (glycoprotein [GP] IIb/IIIa) plays a fundamental role in atherothrombosis. The human platelet antigen (HPA) -1 and the HPA-3 are the most extensively studied polymorphisms of GPIIIa and GPIIb, respectively. This study was designed to test, in a large population, the hypothesis that these polymorphisms represent a risk factor for the occurrence of coronary artery disease (CAD) and myocardial infarction (MI).Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (CAD, n = 998) and those with old or acute MI constituted the group with MI (MI, n = 793). As controls served subjects, matched with patients for age and sex, with neither angiographic CAD nor symptoms or signs of MI (matched controls [MC], n = 340) as well as a group of blood donors without cardiac symptoms or signs of CAD (BD, n = 104). Genotype distribution was similar across the groups; HPA-1a/a: HPA-1a/b: HPA-1b/b was 75.0%: 22.1%: 2.9% in BD, 72.6%: 24.7%: 2.6% in MC, 70.5%: 26.8%: 2.7% in CAD, and 70.7%: 26.4%: 2.9% in MI; HPA-3a/a: HPA-3a/b: HPA-3b/b was 39.4%: 40.4%: 20.2% in BD, 33.5%: 50.0%: 16.5% in MC, 35.0%: 46.4%: 17.0% in CAD, and 37.1%: 48.0%: 16.5% in MI. There was no interaction between these polymorphisms, nor between each of these polymorphisms and other risk factors.Thus, the HPA-1 and HPA-3 polymorphisms are neither separately nor in concert associated with any measurable increase of the risk for CAD or MI in angiographically evaluated subjects.

A patch-clamp study was done to characterize the recently found GABAergic (i.e. gamma-aminobutyric acid) inhibitory synaptic channels of crayfish deep extensor abdominal muscle. Outside-out patches were rapidly activated by GABA to measure the dose/response curves for the open probability of the channels, Po, and the rise time, tr, (time from Po = 0.1 to Po = 0.9). In some of the patches the GABA-activated currents decayed due to desensitization and such patches were not studied further. Rare channel openings were elicited with 0.1 mM GABA. The Po at this low concentration of GABA was 0.0005 to 0.01. Application of 10 mM GABA was necessary to reach the maximal Po of 0.9. The slope of the dose/response relationship in the double logarithmic plot was 5.4 +/- 1.1 (mean +/- SD; n = 9) between 0.1 mM and 0.2 mM GABA. The plot of tr versus GABA concentration had a peculiar shape, recently found to be characteristic for positive cooperativity of the binding sites. tr increased from a minimum at 10 mM GABA with declining concentrations of GABA and reached a peak at 0.4 mM GABA. Below 0.4 mM GABA, tr decreased again. With 0.2 mM GABA tr was 0.40 +/- 0.1 (mean +/- SD; n = 4) of the peak value measured at 0.4 mM GABA. Simulations were compared with the experimental results and a linear reaction scheme with five binding sites for GABA was established to describe the dose/response curves for Po and tr.