The Potassium Channel Subunit Kvβ1 is Required for Synaptic Facilitation

Abstract

Analysis of the presynaptic action potentials (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 Kv{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 Kv{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 Kv channels in synaptic facilitation at small presynaptic terminals of the hippocampal neurons upstream of exocytic machinery. SignificanceNerve terminals generally engage in two opposite and essential forms of synaptic plasticity (facilitation or depression) during high frequency stimulation that play critical roles in learning and memory. Measurements of the electrical impulses (action potentials) underlying these two forms of plasticity has been difficult in small nerve terminals due to their size. In this study we deployed a combination of optical measurements of vesicle fusion and membrane voltage to overcome this previous size barrier. Here, we found a unique molecular composition of Kv1 channel {beta}-subunits that causes broadening of the presynaptic action essential to synaptic facilitation. Disruption of the Kv{beta}1 inactivation mechanism switches excitatory nerve terminals into a depressive state, without any disruption to initial probability of vesicle fusion.