AB31-3:Factors required for graded calcium release in a simplified computational model of the dyadic junction: Importance of junctional variation

In cardiomyocytes, the calcium (Ca) sensitivity of sarcoplasmic reticulum (SR)-bound ryanodine receptor (RyR) channels leads to autocatalytic release of the SR Ca load. Experimental whole-cell data show release from SR to be a high-gain, graded response to current through voltage-dependent L-type Ca channels; at the subcellular level these stimulus/response interactions are largely limited to the segregated microdomains of dyadic junctions. Many present-day models can reproduce this whole-cell behavior through detailed biophysical modeling, but say little about the essential underlying mechanism.