The Influence of Ryanodine Receptors’ Non-uniform Arrangement on the Probability of Ca$$^{2+}$$ Sparks

Abstract

AbstractMany essential physiological processes are controlled by calcium. Ca\(^{2+}\) sparks are the elementary events of calcium release from the sarcoplasmic reticulum (SR) via groups of ryanodine receptors (RyRs). Studying Ca\(^{2+}\) sparks is of great importance to life sciences. Recent experimental studies have shown that RyRs have a non-uniform arrangement in calcium release units (CRUs); however, very little literature takes this fact into account. In this work, we model calcium sparks from CRUs with non-uniform arrangements of RyRs. We show that both parameters that describe the distance between the channels (\(\lambda _{\max }\)) and the clustering of channels (\(N_c\)) correlate well with the spark probability \(P_{s}\) (\(\approx \)90 and 80%, respectively). This result demonstrates that channels cannot be divided into non-interacting RyR clusters inside CRUs. The results of Monte Carlo simulations show that model parameters of RyR gating and calcium diffusion affect \(P_{s}\) and the correlation between \(P_{s}\) and \(\lambda _{\max }\) or \(N_c\) at different RyR arrangements.KeywordsCalcium sparksCalcium dynamicsRyanodine receptors