Three dimensional coupled reaction–diffusion modeling of calcium and inositol 1,4,5-trisphosphate dynamics in cardiomyocytes

Abstract

Nanoparticles have shown great promise in improving cancer treatment efficacy by changing the intracellular calcium level through activation of intracellular mechanisms. One of the mechanisms of the killing of the cancerous cell by a nanoparticle is through elevation of the intracellular calcium level. Evidence accumulated over the past decade indicates a pivotal role for the IP₃ receptor mediated Ca²⁺ release in the regulation of the cytosolic and the nuclear Ca²⁺ signals. There have been various studies done suggesting the role of IP₃ receptors (IP₃R) and IP₃ production and degradation in cardiomyocytes. In the present work, we have proposed a three-dimensional unsteady-state mathematical model to describe the mechanism of cardiomyocytes which focuses on evaluation of various parameters that affect these coupled dynamics and elevate the cytosolic calcium concentration which can be helpful to search for novel therapies to cure these malignancies by targeting the complex calcium signaling process in cardiomyocytes. Our study suggests that there are other factors involved in this signaling which can increase the calcium level, which can help in finding treatment for cancer. The cytosolic calcium level may be controlled by IP₃ signaling, leak, source influx of calcium (σ) and maximum production of IP₃ (V_P). We believe that the proposed model suggests new insight into finding treatment for cancer in cardiomyocytes through elevation of the cytosolic Ca²⁺ concentration by various parameters like leak, σ, V_P and especially by other complex cell signaling dynamics, namely IP₃ dynamics.