Human inward rectifier potassium channels in chronic and postoperative atrial fibrillation.
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.


CONCLUSIONS
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.
Dobrev
Dobromir
D
Department of Pharmacology and Toxicology, Carl Gustav Carus Medical School, Dresden University of Technology, Dresden, Germany. dobrev@rcs.urz.tu-dresden.de
Wettwer
Erich
E
Kortner
Ariane
A
Knaut
Michael
M
Schüler
Stephan
S
Ravens
Ursula
U
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000704:Analysis of Variance; D001281:Atrial Fibrillation / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016009:Chi-Square Distribution; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006331:Heart Diseases / Q000150:complications / Q000601:surgery; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D019616:Thoracic Surgical Procedures
C454420:G-protein beta3 subunit; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020962:Heterotrimeric GTP-Binding Proteins; D000109:Acetylcholine