Does Ca entry by routes other than the L-type Ca current trigger CICR?
The work reviewed in the previous section suggests that the L-type Ca channel is the trigger for s.r. Ca release. It has, however, been suggested that Ca entry on the Na–Ca exchange may also trigger release. 2.2.1 Ca entry on Na–Ca exchange produced by a local increase of Na Leblanc and Hume [14]showed that, even when the L-type current was inhibited, depolarization could produce s.r. Ca release. This Ca release required Na entry into the cell through a TTX-sensitive channel and also the presence of extracellular calcium. They explained this as resulting from (i) Na entry through the TTX-sensitive channels followed by (ii) Na efflux and Ca entry on Na–Ca exchange. As pointed out subsequently, the expected Na entry via the TTX-sensitive channel would produce a very small increase of mean cytoplasmic Na concentration which would be insufficient to affect the Na–Ca exchange. If the Na–Ca exchange is to sense a significant increase of [Na+]i then the Na entry must be into a small fraction
