Involvement of ryanodine receptors in IP3-mediated calcium signalling in neurons

Phospholipase C (PLC)-coupled metabotropic receptors trigger the release of intracellular Ca2+ through activation of IP3 receptors (IP3Rs). Increasing evidence suggests that they can also and perhaps more efficiently mobilize Ca2+ through ryanodine receptors (RyRs). We constructed a model allowing a variable PLC stimulation level (via the parameter γ) as well as a variable involvement of RyRs (via the parameter A). The sole presence of RyRs (A ≠ 0) affected the basal Ca2+ concentration [Ca2+]i. To keep Ca2+ below 160 nM, we fixed the upper limit of A to 0.2, a value that is compatible with the numerical ratio between RyRs and IP3Rs in cerebellar Purkinje neurons. Metabotropic responses were simulated by abruptly raising the value of γ to various levels. In the absence of RyRs, the model starts to oscillate with γ = 0.4. For lower levels of PLC stimulation (γ ≤ 0.3), the presence of RyR is capable of triggering an oscillatory signal. When A ≤ 0.18, the frequency of the Ca2+ oscillations augments from 0.1 to 1.3 Hz as a function of γ. Conversely, as the frequency increases, the amplitude of the oscillations is reduced from 1 μM to 50 nM. With higher values of A, the oscillating pattern is definitively inhibited. It is concluded that RyRs have the potentiality to strikingly affect the temporal pattern of the Ca2+ signalling triggered by IP3-related metabotropic responses.