mitochondria-dependent post-tetanic potentiation at the rat calyx of Held

12 Developmental changes in Ca 2+ clearance and short-term plasticity 13 14 15 Abstract 26 27 The sensitivity of post-tetanic potentiation (PTP) to high frequency stimulation (HFS) steeply decays during 28 the first two postnatal weeks. We investigated the underlying mechanisms for the developmental change of PTP 29 induced by HFS (100 Hz, 2 sec) at postnatal days 4-6 and 9-11 at the rat calyx of Held synapse. Low 30 concentration tetraphenylphosphonium (2 μM), an inhibitor of mitochondrial Na + /Ca 2+ exchanger, suppressed 31 the amount of post-tetanic residual calcium and PTP to a larger extent at the immature calyx synapse, indicating 32 a developmental reduction of mitochondrial contribution to PTP. The higher amount of mitochondrial Ca 2+ 33 uptake during HFS and consequent post-tetanic residual Ca 2+ at the immature calyx of Held was associated 34 with higher peak of HFS-induced Ca 2+ transients, most likely because the mitochondrial Ca 2+ uptake during 35 HFS was supra-linearly dependent on the presynaptic [Ca 2+ ] level. Probing into the contribution of Na + /Ca 2+ 36 exchangers to calcium clearance, we found a specific upregulation of the K +-dependent Na + /Ca 2+ exchanger 37 (NCKX) activity in the mature calyx of Held. We conclude that the upregulation of NCKX limits the Ca 2+ 38 buildup and inhibits mitochondrial Ca 2+ uptake during HFS, which in turn results in the reduction of post-tetanic 39 residual Ca 2+ and PTP at the mature calyx of Held synapse.