Calcium and potassium currents in cells from adult and aged canine right atria.
BACKGROUND
Action potential (AP) contours vary considerably between normal adult and aged right atrial fibers. The ionic bases for these differences remain unknown. Therefore we studied Ca(2+) and K(+) currents in cells from adult and aged canine right atria (RA).


RESULTS
We used whole cell patch clamp recording techniques to measure L-type Ca(2+) currents (I(CaL)) with either Ca(2+) or Ba(2+) (3 mM) as the charge carrier, and both the transient outward (I(to)) and sustained potassium currents (I(sus)) in cells dispersed from normal adult (Adult, 2-5 years) and older dogs (Aged, >8 years). There is a significant reduction in peak I(CaL) (47%) and I(BaL) (43%) in Aged cells, yet differences in I(BaL) disappear with maximal beta adrenergic stimulation (isoproterenol, 1 microM). Composite I(to) and I(sus) densities were significantly increased in the Aged versus Adult cell group (by 31 and 27% at +50 mV, respectively). I(to) decay during a maintained depolarization was slowed in Aged cells. Furthermore, I(to) steady-state inactivation curve was shifted positively in Aged cells. Finally, composite I(to) and I(sus) currents of Aged cells were more sensitive to tetraethylammonium chloride (TEA), a specific inhibitor of some types of K(+) currents. In the presence of TEA (5 mM), I(to) in Aged cells was significantly greater than that in Adult cells.


CONCLUSIONS
Ionic currents differ in Aged versus Adult right atrial cells, such that a reduced Ca(2+) current and augmented outward currents could contribute significantly to the altered AP contour of the Aged RA cell. Adrenergic stimulation appears to restore Ba(2+) currents in Aged cells. Finally, an augmented TEA sensitive current plays a role in changes of I(sus) in Aged right atrial cells.
Dun
Wen
W
Departments of Pharmacology and Pediatrics, Center for Molecular Therapeutics, Columbia University, New York, NY 10032, USA.
Yagi
Takuya
T
Rosen
Michael R
MR
Boyden
Penelope A
PA
D000200:Action Potentials / Q000187:drug effects*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006325:Heart Atria; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D002614:Chelating Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D001464:Barium; D004533:Egtazic Acid; D019789:Tetraethylammonium; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D007545:Isoproterenol; D002118:Calcium