Comparison of sarcoplasmic reticulum Ca2+-ATPase function in human, dog, rabbit, and mouse ventricular myocytes

It has been reported that sarcoplasmic reticulum (SR) Ca2+ uptake is more rapid in rat than rabbit ventricular myocytes, but little information is available on the relative SR Ca2+ uptake activity in others species, including humans. We induced Ca2+ transients with a short caffeine pulse protocol (rapid solution switcher, 10 mM caffeine, 100 ms) in single ventricular myocytes voltage clamped (-80 mV) with pipettes containing 100 μM fluo-3 and nominal 0 Ca2+, in 0 Na+o/0 Ca2+o solution to inhibit Na/Ca exchange. SR in non-paced human, dog, rabbit, and mouse ventricular myocytes could be readily loaded with Ca2+ under our experimental conditions with a pipette [Ca2+] = 100 nM. Resting [Ca2+]i was similar in four types of ventricular myocytes. Activation of the Ca2+-release channel with a 100-ms caffeine pulse produced a rise in [caffeine]i to slightly above 2 mM, the threshold for caffeine activation of Ca2+ release. This caused a similar initial rate of rise and peak [Ca2+]i in the four types of ventricular myocytes. However, there were significant differences in the duration of the plateau (top 10%) [Ca2+]i transients and the time constant of the [Ca2+]i decline (reflecting activity of the SR Ca2+-ATPase), with values for human > dog > rabbit > mouse. In paced myocytes under physiologic conditions, SR Ca2+ content was greater in mouse than in rabbit myocytes, while peak ICa,L was smaller in mouse. These findings confirm substantial species difference in SR Ca2+-ATPase activity, and suggest that the smaller the animal and the more rapid the heart rate, greater the activity of the SR Ca2+-ATPase. In addition, it appears that substantial species differences exist in the degree of SR Ca2+ loading and ICa,L under physiologic conditions.