In both humans and animals the effectiveness of beta-adrenergic stimulation to augment the heart contraction strength declines with aging. We have investigated cellular mechanisms that may underlie the aging deficit. Twitch amplitude (TA), (%rest cell length), measured via photodiode array and cytosolic Ca2+ transient, indexed as transient in Indo-1 fluorescence ratio 410/940 micro(m) (IF) were measured in single ventricular myocytes of rats of varying age during electrical stimulation at 23 degrees C. The L type Ca2+ current (I(Ca), pA/pF) was measured in additional cells during voltage clamp from -40 to 0 mV for 200 msec at 0.5 Hz (CsCl, 120, ATP, 3, and EGTA 10 mM in pipette; CsCl 5, and Ca 1 mM in bath). With aging the maximum TA, IF and ICa response to NE (10-7M) are blunted. A (n=85), each age) IF (n=85, each age) Control (C) % C NE** Control (C) % C NE* 3 Mo 6.27+/-0.32 222.73+/-9.33 0.200+/-0.009 193.77+/-10.44 8 Mo 6.71+/-0.30 174.38+/-7.66 0.225+/-0.012 170.17+/-14.10 24 Mo 6.63+/-0.44 139.00+/-9.98 0.260+/-0.012 144.36+/-10.38 I(Ca) (n=20, each age) Control (C) % C NE** 3 Mo 5.32+/-0.53 235.83+/-20.19 8 Mo 5.36+/-0.42 179.46+/-12.79 24 Mo 5.33+/-0.61 156.71+/-14.07 Age effect *p<0.02; **p<0.001. Thus, the blunted Ta and CaT responses to NE with aging are due to a failure to sufficiently augment Ca2+ influx via I(Ca) to trigger Ca2+ release from the sarcoplasmic reticulum (SR) and to Ca2+ load the SR.
