In these frog synapses, many of the calcium sensors for release and BK channels are far enough from calcium channels that a slow-acting calcium blocker like EGTA can reduce their activity, meaning they don't sit right next to the channels.
Evidence from Studies
No evidence studies found yet.
What Would Prove This
Per GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this claim, ordered from strongest to weakest.
Whether the proportion of EGTA-sensitive release sensors is conserved across developing vertebrate synapses and correlates with microdomain architecture.
A systematic review and meta-analysis of all studies using EGTA/BAPTA differential sensitivity to infer sensor distance from calcium channels in vertebrate synapses, with standardized chelator concentrations and release quantification methods.
Whether experimentally increasing the distance between calcium channels and release sensors reduces EGTA sensitivity.
A double-blind experiment in Xenopus varicosities using optogenetic tethering to move synaptotagmin (release sensor) 50 nm farther from calcium channels, compared to controls, measuring EPSC sensitivity to 40 μM EGTA-AM in 60+ synapses with blinding to construct.
Whether the proportion of EGTA-sensitive release increases during synaptic maturation in Xenopus.
A longitudinal cohort study measuring the percentage of EPSC inhibition by 40 μM EGTA-AM in 100+ Xenopus varicosities from day 1 to day 14 post-culture, with standardized protocols and blinding to age.
Whether synapses with disrupted calcium channel clustering show increased EGTA sensitivity.
A case-control study comparing 30 Xenopus varicosities with CRISPR knockdown of RIM protein (disrupts clustering) to 30 controls, measuring the percentage of EPSC inhibition by 40 μM EGTA-AM under identical calcium influx protocols.
Whether 20–50% of EPSC and BK current are inhibited by 40 μM EGTA-AM in Xenopus varicosities at day 3 post-culture.
A cross-sectional measurement of EPSC and BK current inhibition by 40 μM EGTA-AM in 120+ Xenopus varicosities at day 3 post-culture, with standardized application protocols and blinding to treatment.