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). METHODS AND 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.
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 canineright atria (RA). METHODS AND 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.