Sodium current function in adult and aged canine atrial cells

Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, New York Submitted 17 January 2006 ; accepted in final form 17 March 2006 The incidence of atrial fibrillation increases with age, but it is unknown whether there are changes in the intrinsic function of Na + currents in cells of the aged atria. Thus, we studied right (RA) and left (LA) atrial cells from two groups of dogs, adult and aged (>8 yr), to determine the change in Na + currents with age. In this study all dogs were in normal sinus rhythm. Whole cell voltage clamp techniques were used to compare the Na + currents in the two cell groups. Immunocytochemical studies were completed for the Na + channel protein Na v 1.5 to determine whether there was structural remodeling of this protein with age. In cells from aged animals, we found that Na + currents are similar to those we measured in adult atria. However, Na + current ( I Na ) density of the aged atria differed depending on the atrial chamber with LA cell currents being larger than RA cell currents. Thus with age, the difference in I Na density between atrial chambers remains. I Na kinetic differences between aged and adult cells included a significant acceleration into the inactivated state and an enhanced use-dependent decrease in peak current in aged RA cells. Finally, there is no structural remodeling of the cardiac Na + channel protein Na v 1.5 in the aged atrial cell. In conclusion, with age there is no change in I Na density, but there are subtle kinetic differences contributing to slight enhancement of use dependence. There is no structural remodeling of the fast Na + current protein with age. ion channels; remodeling; arrhythmias; atrial fibrillation; age Address for reprint requests and other correspondence: P. A. Boyden, Dept. of Pharmacology, Columbia College of Physicians and Surgeons, 630 W. 168th St., New York, NY 10032 (e-mail: pab4{at}columbia.edu )