Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 47, Pages 29937-29947Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2000790117
Keywords
synapse; potassium channel; action potential; exocytosis; synaptic plasticity
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Funding
- Esther A. and Joseph Klingenstein Fund
- NSF [IOS 1750199]
- US Department of Education Graduate Assistance in Areas of National Need Grant [P200A150059]
- NIH [F31NS110192-01A1]
- P20 NIGMS Grant [GM113132]
- [R00-NS099469]
- [P20-GM113132]
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Analysis of the presynaptic action potential's (AP(syn)) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high-resolution optical recordings of membrane potential, exocytosis, and Ca2+ in cultured hippocampal neurons. These recordings revealed a critical and selective role for K(v)1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic K(v)1 channel inactivation was mediated by the K-v beta 1 subunit and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of K-v beta 1 blocked all broadening of the APsyn during high-frequency stimulation and eliminated synaptic facilitation without altering the initial probability of vesicle release. Thus, using all quantitative optical measurements of presynaptic physiology, we reveal a critical role for presynaptic K-v channels in synaptic facilitation at presynaptic terminals of the hippocampus upstream of the exocytic machinery.
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