Sodium current function in adult and aged canine atrial cells.
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.
Baba
Shigeo
S
Department of Pharmacology, Center for Molecular Therapeutics, Columbia University, New York, NY, USA.
Dun
Wen
W
Hirose
Masanori
M
Boyden
Penelope A
PA
D000375:Aging / Q000502:physiology*; D000818:Animals; D002469:Cell Separation; D004285:Dogs; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D007150:Immunohistochemistry; D007700:Kinetics; D008856:Microscopy, Fluorescence; D009124:Muscle Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000378:metabolism*
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels