The potassium channel subunit Kvβ1 serves as a major control point for synaptic facilitation
| Autor: | Scott A Alpizar, Lauren C. Panzera, Genaro E. Olveda, Morven Chin, Michael B. Hoppa, Robert A. Hill, In Ha Cho |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Intravital Microscopy Large-Conductance Calcium-Activated Potassium Channel beta Subunits Primary Cell Culture Neural facilitation Presynaptic Terminals Hippocampus Hippocampal formation Exocytosis Synapse 03 medical and health sciences Mice 0302 clinical medicine action potential synapse Animals Cells Cultured Membrane potential Elapid Venoms Multidisciplinary synaptic plasticity Kv1.3 Potassium Channel Neuronal Plasticity Chemistry Pyramidal Cells Optical Imaging Biological Sciences Synaptic Potentials Potassium channel Rats 030104 developmental biology Gene Knockdown Techniques Synaptic plasticity Excitatory postsynaptic potential Calcium Female Neuroscience 030217 neurology & neurosurgery potassium channel |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance Nerve terminals generally engage in two opposite and essential forms of synaptic plasticity (facilitation or depression) that play critical roles in learning and memory. While the molecular components of both types of terminals are similar with regards to vesicle fusion, much less is known about their molecular control of electrical signaling. Measurements of the electrical impulses (action potentials) underlying these two forms of plasticity have been difficult in small nerve terminals due to their size. In this study we deployed optical physiology measurements to overcome this size barrier. Here, we identify a unique mechanism (Kvβ1 subunit) that enables broadening of the presynaptic action potentials that selectively supports synaptic facilitation, but does not alter any other aspects of nerve terminal function. Analysis of the presynaptic action potential’s (APsyn) 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 Kv1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons. Presynaptic Kv1 channel inactivation was mediated by the Kvβ1 subunit and had a surprisingly rapid onset that was readily apparent even in brief physiological stimulation paradigms including paired-pulse stimulation. Genetic depletion of Kvβ1 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 Kv channels in synaptic facilitation at presynaptic terminals of the hippocampus upstream of the exocytic machinery. |
| Databáze: | OpenAIRE |
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