RyRs do not contribute to calcium signal due to N and P/Q type calcium channels.

<p>A) Representative trace showing inhibition of the HiK response by ryanodine (20 µM), conotoxin GVIA (800 nM) and conotoxin GVIA+ ryanodine. B) Analysis using a one-way ANOVA with Bonferroni’s post-hoc analysis of the inhibition of the peak amplitude for each condition shows enhanced inhibition of the HiK response during co-application of conotoxin GVIA and ryanodine (n = 6, **p = 0.009) compared to the inhibition due to either N type channels or ryanodine receptors alone. C) Representative trace showing inhibition of the HiK response by agatoxin (300 nM), ryanodine (20 µM) and agatoxin+ryanodine. D) Co-application of agatoxin and ryanodine significantly increases inhibition of the peak amplitude for the calcium-influx response (n = 7, *p = 0.018) compared to the level of inhibition due to blocking either P/Q type channels or ryanodine receptors.