Developmental upregulation of presynaptic NCKX underlies the decrease of mitochondria-dependent posttetanic potentiation at the rat calyx of Held synapse

摘要

The sensitivity of posttetanic potentiation (PTP) to high-frequency stimulation (HFS) steeply decays during the first 2 postnatal weeks. We investigated the underlying mechanisms for the developmental change of PTP induced by HFS (100 Hz, 2 s) at postnatal days 4-6 and 9-11 at the rat calyx of Held synapse. Low-concentration tetraphenylphosphonium (2 /xM), an inhibitor of mitochondrial Na~+/Ca~(2+) exchanger, suppressed the amount of posttetanic residual Ca~(2+) and PTP to a larger extent at the immature calyx synapse, indicating a developmental reduction of mitochondrial contribution to PTP. The higher amount of mitochondrial Ca~(2+) uptake during HFS and consequent posttetanic residual Ca~(2+) at the immature calyx of Held was associated with higher peak of HFS-induced Ca~(2+) transients, most likely because the mitochondrial Ca~(2+) uptake during HFS was supralinearly dependent on the presynaptic resting Ca~(2+) level. Probing into the contribution of Na~+/Ca~(2+) exchangers to Ca~(2+) clearance, we found a specific upregulation of the K~+-dependent Na~+/Ca~(2+) exchanger (NCKX) activity in the mature calyx of Held. We conclude that the upregulation of NCKX limits the Ca~(2+) buildup and inhibits mitochondrial Ca~(2+) uptake during HFS, which in turn results in the reduction of posttetanic residual Ca~(2+) and PTP at the mature calyx of Held synapse.