Calcium concentration and movement in the diadic cleft space of the cardiac ventricular cell

Abstract

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.