UNASSIGNED: In the heart, electrical stimulation of cardiac myocytes increases the open probability of sarcolemmal voltage-sensitive @entity141 channels and flux of @entity141 into the cells. This increases @entity141 binding to ligand-gated channels known as @entity8452 receptors ( @entity23963 ). Their openings cause cell-wide release of @entity141 , which in turn causes muscle contraction and the generation of the mechanical force required to pump blood. In resting myocytes, @entity23963 s can also open spontaneously giving rise to spatially-confined @entity141 release events known as "sparks." @entity23963 s are organized in a lattice to form clusters in the junctional sarcoplasmic reticulum membrane. Our recent work has shown that the spatial arrangement of @entity23963 s within clusters strongly influences the frequency of @entity141 sparks. We showed that the probability of a @entity141 spark occurring when a single @entity23963 in the cluster opens spontaneously can be predicted from the precise spatial arrangements of the @entity23963 s. Thus, "function" follows from "structure." This probability is related to the maximum eigenvalue (  1) of the adjacency matrix of the @entity23963 cluster lattice. In this work, we develop a theoretical framework for understanding this relationship. We present a stochastic contact network model of the @entity141 spark initiation process. We show that   1 determines a stability threshold for the formation of @entity141 sparks in terms of the @entity23963 gating transition rates. We recapitulate these results by applying the model to realistic @entity23963 cluster structures informed by super-resolution stimulated emission depletion (STED) microscopy. Eigendecomposition of the linearized mean-field contact network model reveals functional subdomains within @entity23963 clusters with distinct sensitivities to @entity141 . This work provides novel perspectives on the cardiac @entity141 release process and a general method for inferring the functional properties of transmembrane receptor clusters from their structure.

On the Adjacency Matrix of XXXX Cluster Structures.

@entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity8452 :: ('MESH:D012433', 'Chemical') :: ['ryanodine'] @entity23963 :: ('6262', 'Gene') :: ['RyR2']
@entity23963 :: (6262,Gene) :: ['RyR2']
