Figure 5. Modelling the contributions of Ca²⁺ current facilitation and residual Ca²⁺ to paired-pulse facilitation.

Aa, presynaptic whole-cell Ca²⁺ currents (I_Ca) recorded at an interstimulus interval of 10 ms. The Ca²⁺ current integral is highlighted in red. Ab, the inverted Ca²⁺ current waveforms (black traces), and the waveforms of local [Ca²⁺]_i signals inferred by the ‘five-site model’ (blue, red and dashed green traces). The blue trace represents the ‘local’[Ca²⁺]_i waveform that predicted the transmitter release rate during the first pulse (see Ac). The red and green traces are simulated local [Ca²⁺]_i waveforms for the second pulse, which take into account Ca²⁺ current facilitation alone (‘Q’; dashed red trace; hardly visible), or Ca²⁺ current facilitation plus a linear summation of residual free [Ca²⁺]_i and the local [Ca²⁺]_i signal (‘Q+R’; red trace), or both mechanisms plus an assumed supra-linearity in the summation of the [Ca²⁺]_i signals (‘Q+R+S’; dashed green trace). Ac, measured transmitter release rates (black trace) and model fits, under the same assumptions and with the same colour code as shown in Ab. Note that Ca²⁺ current facilitation together with a direct action of residual free [Ca²⁺]_i (red trace) explains only 42% of the transmitter release facilitation in this example, as visualized by the red arrow. B, peak transmitter release rates as predicted by driving the five-site model (black trace; parameters as in Felmy et al. 2003), and the allosteric model (dashed black trace; parameters as in Lou et al. 2005) with local [Ca²⁺]_i waveforms as shown in Ab, over a wide range of [Ca²⁺]_i amplitudes. The red lines with circles and squares indicate slopes in double-log coordinates at two ranges of [Ca²⁺]_i. Note that a near-maximal slope of the five-site model is only reached at exceedingly low [Ca²⁺]_i (slope, 4.8 at 1–1.5 μm[Ca²⁺]_i). The grey line shows the prediction of the five-site model with the same parameter set, but using square [Ca²⁺]_i elevations. The rightward shift of the predicted transmitter release rates driven by [Ca²⁺]_itransients is caused by the briefness of the rise and fall of the local [Ca²⁺]_i signal.