| Abstract: | This paper extends the model for Ca movement in the cardiac ventricular cell from the diadic cleft space to the entire sarcomere. The model predicts the following: 1) Shortly after SR release there is a Ca] gradient >3 orders of magnitude from cleft center to M-line which, 50 ms after release, is still >30. Outside the cleft, 40 ms after cessation of release, the axial gradient from Z to M-line is >3. 2) At the end of SR release, >50% of the total Ca released is bound to low-affinity inner sarcolemmal phospholipid binding sites within the cleft. 3) Halving the SR release almost doubles the fraction of release removed from the cell via Na/Ca exchange and reduces average sarcomeric free Ca] by 70%. 4) Adding 100 microM fluo-3, which doubles the buffering capacity of the cytoplasm, reduces peak average sarcomeric Ca] by >50% and increases the initial half-time for Ca] decrease by approximately twofold. 5) A typical Ca "spark" can be generated by an SR release 20% of maximum (4 x 10(-20) moles) over 2 ms. Fluo-3 (100 microM) significantly "shrinks" the spark. 6) The "spark" is a consequence of elementary events within the diadic cleft space. For example, removal of cleft binding sites would cause average sarcomeric Ca to increase by >10 fold, fall 10 times more rapidly, decrease latency for appearance of the spark by >20 times, and reduce spark duration by 85%. 7) Dividing SR Ca release between cleft and corbular SR produces a secondary Ca] peak and a "flattening" of the sarcomeric Ca] transient. These changes probably could not be resolved with current confocal microscopic techniques. |
