Possible role of Ca2+ dependent ATPase in determining the relationship between stimulation frequency and action potential duration in the myocardial fibre

At present, action potential duration (APD) is considered to be dependent on the activation of the transient outward current. We applied a stimulation frequency (SF) pattern which was continuously and linearly increased (from the third stimulus on, every stimulus was applied 40 ms earlier than the previous one). Our previous results (Stanciu and Stanciu, 1995) have shown both a decrease of APD--in the interval between 0.5 Hz and 2 Hz, and in the one between 4 Hz and 8 Hz, and an increase of APD--in the interval between 2 Hz and 4 Hz. Triiodothyronine, which stimulates Ca2+ dependent ATPase, has positive effects on APD for all SF, ranging from 0.5 Hz to 6 Hz. On the contrary, increasing the pH value (from 7.4 to 8.6), which prevents Ca2+ binding to membrane proteins, determines a decrease of APD for the same SF levels. Therefore, we advance the assumption that there should be some attached protein molecules, having a role in Ca2+ storage, on the external side of the sarcolemmal membrane. In this case, it is the sarcolemmal Ca2+ dependent ATPase which performs the loading of those stores. The loading up to saturation state is accomplished during a time lapse that depends on the working rate of the Ca2+ dependent ATPase. The premature occurrence of a stimulus finds the store only partially loaded with Ca2+, which may explain the decrease in APD associated with the increase in SF. The continuous and linear increase of SF results in a high internal Ca2+ concentration and--consequently--in the stimulation of Ca2+ dependent ATPase. That explains the APD increase for SF ranging between 2 Hz and 4 Hz. The same pattern of SF increase (continuos and linear), but using frequencies higher than 4 Hz, results in an overflow of the maximal operating capacity of the Ca2+ dependent ATPase and also in the reduction of APD amplitude.