PT  - JOURNAL ARTICLE
AU  - Monica S. Thanawala
AU  - Wade G. Regehr
TI  - Presynaptic Calcium Influx Controls Neurotransmitter Release in Part by Regulating the Effective Size of the Readily Releasable Pool
AID  - 10.1523/JNEUROSCI.4031-12.2013
DP  - 2013 Mar 13
TA  - The Journal of Neuroscience
PG  - 4625--4633
VI  - 33
IP  - 11
4099  - http://www.jneurosci.org/content/33/11/4625.short
4100  - http://www.jneurosci.org/content/33/11/4625.full
SO  - J. Neurosci.2013 Mar 13; 33
AB  - The steep calcium dependence of synaptic strength that has been observed at many synapses is thought to reflect a calcium dependence of the probability of vesicular exocytosis (p), with the cooperativity of three to six corresponding to the multiple calcium ion binding sites on the calcium sensor responsible for exocytosis. Here we test the hypothesis that the calcium dependence of the effective size of the readily releasable pool (RRP) also contributes to the calcium dependence of release at the calyx of Held synapse in mice. Using two established methods of quantifying neurotransmitter release evoked by action potentials (effective RRP), we find that when calcium influx is changed by altering the external calcium concentration, the calcium cooperativity of p is insufficient to account for the full calcium dependence of EPSC size; the calcium dependence of the RRP size also contributes. Reducing calcium influx by blocking R-type voltage-gated calcium channels (VGCCs) with Ni2+, or by blocking P/Q-type VGCCs with ω-agatoxin IVA also changes EPSC amplitude by reducing both p and the effective RRP size. This suggests that the effective RRP size is dependent on calcium influx through VGCCs. Furthermore, activation of GABAB receptors, which reduces presynaptic calcium through VGCCs without other significant effects on release, also reduces the effective RRP size in addition to reducing p. These findings indicate that calcium influx regulates the RRP size along with p, which contributes to the calcium dependence of synaptic strength, and it influences the manner in which presynaptic modulation of presynaptic calcium channels affects neurotransmitter release.