Cardiovascular research · 2002
Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation.
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Dobrev Dobromir, Wettwer Erich, Kortner Ariane, Knaut Michael, Schüler Stephan, Ravens Ursula
Аннотация
OBJECTIVE: We showed recently that the 825T allele of the G-protein beta 3-subunit C825T polymorphism is associated with large inward rectifier K(+) currents I(K1) but low acetylcholine-activated K(+) current I(K,ACh) amplitudes. During chronic atrial fibrillation (AF), I(K1) and I(K,ACh) current densities were increased when compared to sinus rhythm (SR). It is unknown whether chronic AF and G beta 3 gene status are independent contributors to atrial K(+) current activity. We measured I(K1) and I(K,ACh) in tissue from AF patients with different G beta 3 genotypes and assessed the relation between the I(K1) and I(K,ACh) amplitudes and the incidence of postoperative AF.
METHODS: We measured the amplitudes of I(K1) and I(K,ACh) in atrial myocytes from 26 patients with sinus rhythm (SR) and from 16 patients with chronic AF (>6 months). The K(+) currents were measured with standard patch-clamp techniques. The G beta 3 gene status of the patients was determined by PCR and restriction analysis.
RESULTS: At -100 mV, the amplitude of I(K1) was larger in AF (10.9+/-1.0 pA/pF, n=49/16, cells/patients) than in SR (6.3+/-0.6 pA/pF, n=68/26, P<0.05), whereas the amplitude of I(K,ACh) was smaller in chronic AF (2.9+/-0.7 pA/pF, n=49/16) than in SR (6.3+/-0.7 pA/pF, n=68/26, P<0.05). These changes were independent of the patient G beta 3 gene status. Eight patients out of 26 in the SR group (31%) developed postoperative AF. When analysed based on incidence of postoperative AF, current amplitudes did not differ significantly.
CONCLUSION: We provide evidence for up-regulation of I(K1) but down-regulation of I(K,ACh) in chronic AF which are independent of G beta 3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered I(K1) and I(K,ACh) at the time of cardiac surgery. Our results suggest that the AF-related changes of I(K1) and I(K,ACh) may be a consequence of or a contributory factor to chronic AF.
METHODS: We measured the amplitudes of I(K1) and I(K,ACh) in atrial myocytes from 26 patients with sinus rhythm (SR) and from 16 patients with chronic AF (>6 months). The K(+) currents were measured with standard patch-clamp techniques. The G beta 3 gene status of the patients was determined by PCR and restriction analysis.
RESULTS: At -100 mV, the amplitude of I(K1) was larger in AF (10.9+/-1.0 pA/pF, n=49/16, cells/patients) than in SR (6.3+/-0.6 pA/pF, n=68/26, P<0.05), whereas the amplitude of I(K,ACh) was smaller in chronic AF (2.9+/-0.7 pA/pF, n=49/16) than in SR (6.3+/-0.7 pA/pF, n=68/26, P<0.05). These changes were independent of the patient G beta 3 gene status. Eight patients out of 26 in the SR group (31%) developed postoperative AF. When analysed based on incidence of postoperative AF, current amplitudes did not differ significantly.
CONCLUSION: We provide evidence for up-regulation of I(K1) but down-regulation of I(K,ACh) in chronic AF which are independent of G beta 3 gene status. Atrial myocytes from patients who are in SR but later develop postoperative AF have no manifestation of altered I(K1) and I(K,ACh) at the time of cardiac surgery. Our results suggest that the AF-related changes of I(K1) and I(K,ACh) may be a consequence of or a contributory factor to chronic AF.
Предметные рубрики MeSH
AcetylcholineAgedAnalysis of VarianceAtrial FibrillationChi-Square DistributionChronic DiseaseFemaleGene ExpressionGenotypeHeart DiseasesHeterotrimeric GTP-Binding ProteinsHumansMaleMiddle AgedPatch-Clamp TechniquesPolymorphism, GeneticPostoperative ComplicationsPotassium ChannelsPotassium Channels, Inwardly RectifyingThoracic Surgical Procedures