title: Sparse but highly efficient Kv3 outpace BKCa channels in action potential repolarization at hippocampal mossy fiber boutons.
abstract: Presynaptic elements of axons, in which action potentials (APs) cause release of neurotransmitter, are sites of high densities and complex interactions of proteins. We report that the presence of K(v)3 channels in addition to K(v)1 at glutamatergic mossy fiber boutons (MFBs) in rat hippocampal slices considerably limits the number of fast, voltage-activated potassium channels necessary to achieve basal presynaptic AP repolarization. The ∼ 10-fold higher repolarization efficacy per K(v)3 channel compared with presynaptic K(v)1 results from a higher steady-state availability at rest, a better recruitment by the presynaptic AP as a result of faster activation kinetics, and a larger single-channel conductance. Large-conductance calcium- and voltage-activated potassium channels (BK(Ca)) at MFBs give rise to a fast activating/fast inactivating and a slowly activating/sustained K(+) current component during long depolarizations. However, BK(Ca) contribute to MFB-AP repolarization only after presynaptic K(v)3 have been disabled. The calcium chelators EGTA and BAPTA are equally effective in preventing BK(Ca) activation, suggesting that BK(Ca) are not organized in nanodomain complexes with presynaptic voltage-gated calcium channels. Thus, the functional properties of K(v)3 channels at MFBs are tuned to both promote brevity of presynaptic APs limiting glutamate release and at the same time keep surface protein density of potassium channels low. Presynaptic BK(Ca) channels are restricted to limit additional increases of the AP half-duration in case of K(v)3 hypofunction, because rapid membrane repolarization by K(v)3 combined with distant calcium sources prevent BK(Ca) activation during basal APs.
authors.affiliation: Institut für Neurophysiologie and Cluster of Excellence NeuroCure, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: Alle
authors.forename: Hisahiko
authors.initials: H
authors.lastname: Kubota
authors.forename: Jörg R P
authors.initials: JR
authors.lastname: Geiger
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D051637:Shaker Superfamily of Potassium Channels / Q000502:physiology; D051670:Shaw Potassium Channels / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002614:Chelating Agents; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels; D051670:Shaw Potassium Channels; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium