Calcium signalling plays a central role in heart cells. With each heart beat, calcium is released from intracellular stores (SR) via RyR channels to trigger contraction. However, calcium signalling is also implicated in controlling the growth of heart cells, as occurs during development, in response to exercise, and in hypertrophic heart disease. This calcium signal triggers gene expression in the nucleus, and occurs via release of calcium through IP3R channels. How these two distinct calcium signals can occur at the same time is not well understood.
Here we present a mathematical model of calcium release through RyRs and IP3Rs which demonstrates that the interaction between these two calcium signalling mechanisms can increase the duty cycle of the cytosolic calcium transient (that is, increase the period during which calcium remains elevated during each cycle). This finding is consistent with recent experiments which showed that an increase in the duration of elevated cytosolic calcium leads to hypertrophy-related gene transcription.
Therefore, our work, together with the recent experimental study, suggests a plausible mechanism for IP3R-dependent hypertrophic signalling by calcium in cardiomyocytes.
This work was conducted by Hilary Hunt, in collaboration with the Soeller (Exeter) and Roderick (Leuven) labs.
H. Hunt, G. Bass, C. Soeller, L. Roderick, V. Rajagopal, E.J. Crampin
How does interaction between RyR and IP3R mediated calcium release shape the calcium transient for hypertrophic signalling in cardiomyocytes?