Langer G A, Peskoff A
Department of Medicine, UCLA School of Medicine 90095-1760, USA.
Biophys J. 1996 Mar;70(3):1169-82. doi: 10.1016/S0006-3495(96)79677-7.
We model the space between the junctional sarcoplasmic reticulum (JSR) membrane and the inner leaflet of the transverse tubular ("T") sarcolemmal (SL) membrane, the diadic cleft, with respect to calcium (Ca) concentration and movement. The model predicts the following: 1) Ca influx via the "L" channel increases [Ca] to 1 microM within a distance of 50 nm from the channel mouth in < 500 microseconds. This is sufficient to trigger Ca release from a domain of 9 "feet." 2) By contrast, "reverse" Na/Ca exchange will increase [Ca] to approximately 0.5 microM throughout the cleft space in 10 ms, sufficient to trigger Ca release, but clearly to a lesser extent and more slowly than the channel. 3) After a 20-ms JSR release into the cleft via the "feet" [Ca] peaks at 600 microM (cleft center) to 100 microM (cleft periphery) and then declines to diastolic level (100 nM) within 150 ms throughout the cleft. 4) The ratio of flux out of the cleft via Na/Ca exchange to flux out of the cleft to the cytosol varies inversely as JSR Ca release. 5) Removal of SL anionic Ca-binding sites from the model will cause [Ca] to fall to 100 nM throughout the cleft in < 1 ms after JSR release ceases. This markedly reduces Na/Ca exchange. 6) Removal from or decreased concentration of Na/Ca exchangers in the cleft will cause [Ca] to fall too slowly after JSR release to permit triggered release upon subsequent excitation.
我们针对钙（Ca）浓度和移动情况，对连接肌浆网（JSR）膜与横管（“T”）肌膜（SL）内膜之间的空间，即二联体裂隙进行建模。该模型预测如下：1）通过“L”型通道的钙内流在不到500微秒的时间内，使距离通道口50纳米范围内的[Ca]增加到1微摩尔/升。这足以触发来自9个“足”区域的钙释放。2）相比之下，“反向”钠/钙交换将在10毫秒内使整个裂隙空间的[Ca]增加到约0.5微摩尔/升，足以触发钙释放，但明显比通道作用的程度小且更缓慢。3）在通过“足”向裂隙进行20毫秒的JSR释放后，[Ca]在裂隙中心达到600微摩尔/升的峰值，在裂隙周边达到100微摩尔/升，然后在整个裂隙内150毫秒内降至舒张水平（100纳摩尔/升）。4）通过钠/钙交换从裂隙流出的通量与从裂隙流出到胞质溶胶的通量之比与JSR钙释放成反比。5）从模型中去除SL阴离子钙结合位点将导致在JSR释放停止后不到1毫秒内，整个裂隙中的[Ca]降至100纳摩尔/升。这显著降低了钠/钙交换。6）从裂隙中去除钠/钙交换体或降低其浓度将导致JSR释放后[Ca]下降过慢，无法在随后的兴奋时引发释放。
