Calcium release and uptake from the cardiac sarcoplasmic reticulum: Experimental and mathematical models

Abstract

Excitation-contraction coupling (ECC) and cardiac muscle force development rely on the regulation of both release (through channels or ryanodine receptors, RyR) and uptake (by an ATPase) of Ca²⁺ by the sarcoplasmic reticulum (SR). In this work, we propose an experimental model in which Ca²⁺ transport is simplified by using a thermodynamic approach to inhibit part of the cellular Ca²⁺ transporters but keeping functional the SR release and uptake as almost sole transporters. Instead of membrane excitation, electrically quiescent cells were stimulated with brief caffeine pulses (10 mM, 0.1 s duration). The method was tested experimentally and the results were compared to mathematical simulations performed by using a modified version of the mathematical model of Ca²⁺ cycling in cardiomyocytes previously proposed [1]. Results indicated that the experimental model is suitable to study properties of the SR-cytosol Ca²⁺ transport in intact cells without significant interference of other competing transporters (e.g. Na⁺/ Ca²⁺ exchanger).