Density and function of inward currents in right atrial cells from chronically fibrillating canine atria.
OBJECTIVE
To determine whether I(Na) and I(CaL) are altered in function/density in right atrial (RA) cells from dogs with chronic atrial fibrillation (cAF dogs, episodes lasting at least 6 days) and whether the changes that occur differ from those in dogs with nonsustained or brief episodes of fibrillation (nAF dogs).


METHODS
Using whole cell voltage clamp, sodium and calcium current density and function were determined in disaggregated RA cells from nAF, cAF and control atria (Con). Ca(2+) currents were studied with either Ca(2+) or Ba(2+) as charge carrier, as well as with either EGTA or BAPTA as the internal solution Ca(2+) chelator.


RESULTS
After rapid atrial pacing, dogs can either fibrillate for short periods of time (nAF) or longer, more sustained periods (cAF). Both the Na(+) and Ca(2+) current decrease in cells of the nAF atria. Na(+) current density remains reduced in cAF cells with some slowing of recovery kinetics. Ca(2+) current density does not further decrease with persistent atrial fibrillation (cAF cells) remaining significantly different from Con cells. However, the difference in density of Ca(2+) currents between nAF and Con cells is negligible when Ba(2+) is charge carrier and when Ca(i) is quickly and effectively chelated with BAPTA. On the contrary, cAF I(BaL) densities remain significantly reduced compared to Con and nAF values when Ba(2+)/BAPTA conditions are used.


CONCLUSIONS
Na(+) current density/function does not recover to Con values in cAF. Further these enhanced Ca(2+)-dependent inactivation processes contribute significantly to the reduction of I(CaL) density observed in nAF cells while reduction of Ca(2+) currents in cAF atria is probably by another mechanism
Yagi
Takuya
T
Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA.
Pu
Jielin
J
Chandra
Parag
P
Hara
Motoki
M
Danilo
Peter
P
Rosen
Michael R
MR
Boyden
Penelope A
PA
D000704:Analysis of Variance; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D007473:Ion Channels / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism
D015220:Calcium Channels; D007473:Ion Channels; D015222:Sodium Channels