NUMERICAL-SIMULATION OF LOCAL CALCIUM MOVEMENTS DURING L-TYPE CALCIUM-CHANNEL GATING IN THE CARDIAC DIAD

Computer simulation was used to investigate the calcium levels after s arcolemmal calcium influx through L-type calcium channels (DHPRs) into the narrow diadic space of cardiac muscle, The effect of various cyto solic and membrane-bound buffers, diad geometry, DHPR properties (open time and current), and surface charge were examined, The simulations showed that phospholipid binding sites on the sarcolemmal membrane are the major buffer affecting free calcium ([Ca2+]) levels in the diad, The inclusion of surface charge effects calculated from Gouy-Chapman t heory resulted in a marked decrease in [Ca2+] levels at all times and a faster decay of [Ca2+] after termination of DHPR influx, For a DHPR current of 200 fA, [Ca2+] at the center of the diad reached peak level s of similar to 73 mu M. In larger diads (greater than or equal to 400 nm diameter), [Ca2+] decayed more slowly than in smaller diads (100-2 00 nm diameter), although peak [Ca2+] levels reached during typical DH PR open times were similar. For a wide range of DHPR single-channel cu rrent magnitudes (\(Ca) = 25-200 fA), [Ca2+] levels in the diad were a pproximately proportional to \(Ca). The decrease in calculated [Ca2+] levels due to the effects of surface charge can be interpreted as resu lting from an effective ''volume expansion'' of the diad space. Furthe rmore, the layer of increased [Ca2+] close to the sarcolemmal membrane can act as a fast buffer.