title: Enhancing the fidelity of neurotransmission by activity-dependent facilitation of presynaptic potassium currents.
abstract: Neurons convey information in bursts of spikes across chemical synapses where the fidelity of information transfer critically depends on synaptic input-output relationship. With a limited number of synaptic vesicles (SVs) in the readily releasable pool (RRP), how nerve terminals sustain transmitter release during intense activity remains poorly understood. Here we report that presynaptic K(+) currents evoked by spikes facilitate in a Ca(2+)-independent but frequency- and voltage-dependent manner. Experimental evidence and computer simulations demonstrate that this facilitation originates from dynamic transition of intermediate gating states of voltage-gated K(+) channels (Kvs), and specifically attenuates spike amplitude and inter-spike potential during high-frequency firing. Single or paired recordings from a mammalian central synapse further reveal that facilitation of Kvs constrains presynaptic Ca(2+) influx, thereby efficiently allocating SVs in the RRP to drive postsynaptic spiking at high rates. We conclude that presynaptic Kv facilitation imparts neurons with a powerful control of transmitter release to dynamically support high-fidelity neurotransmission.
authors: 1] Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada M5G 1X8 [2] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8 [3].
authors: Yi-Mei
authors: YM
authors: Yang
authors: 1] Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, China [2] Department of Medical Engineering, the 180th Hospital of PLA, Quanzhou 362000, China [3].
authors: Wei
authors: W
authors: Wang
authors: 1] Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada M5G 1X8 [2] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors: Michael J
authors: MJ
authors: Fedchyshyn
authors: Institute of Molecular Medicine &PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Zhuan
authors: Z
authors: Zhou
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, China.
authors: Jiuping
authors: J
authors: Ding
authors: 1] Program in Neurosciences and Mental Health, SickKids Research Institute, Toronto, Ontario, Canada M5G 1X8 [2] Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors: Lu-Yang
authors: LY
authors: Wang
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D003412:Cricetulus; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D051662:Kv1.1 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051663:Kv1.2 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051664:Kv1.3 Potassium Channel / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008867:Microtomy; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D051662:Kv1.1 Potassium Channel; D011188:Potassium; D002118:Calcium