The effect of temperature on the rate-dependent decrease of the rat ventricular calcium current

We have investigated the effect of temperature upon the rate-dependent decrease in the L-type Ca2+ current (iCa) in isolated rat ventricular myocytes. Increasing the rate of stimulation from 0.5 to 3.0 Hz for 30s induced a reversible decrease in iCa which was temperature dependent. Compared to control (0.5 Hz), the first beat at 3 Hz was decreased by 38 +/- 7% at 22 degrees C and by 9 +/- 1% at 37 degrees C (mean +/- S.E.M., n = 5, P < 0.05) and, after 30 s of 3 Hz stimulation, iCa was reduced by a further 26 +/- 4 and 21 +/- 2% at 22 and 37 degrees C, respectively. The magnitude of this secondary decline was not significantly different at the two temperatures (P = 0.29). Corroboratory results were obtained from cell-attached patches which also illustrated that the rate-dependent decrease in iCa resulted from a reduction of open channel probability. Paired pulse experiments showed that the greater initial rate-dependent decrease in iCa at 22 degrees C occurred as a result of slower recovery from fast inactivation processes at 22 than at 37 degrees C. Recovery of the channel from fast inactivation was very temperature sensitive with a Q10 of 5.6. In contrast, the secondary, progressive decrease in iCa, which results from incomplete recovery from ultra-slow voltage-dependent inactivation, was similar at the two temperatures and appears to be much less temperature dependent.