title: Presynaptic rat Kv1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion.
abstract: Voltage-gated K+ channels activating close to resting membrane potentials are widely expressed and differentially located in axons, presynaptic terminals and cell bodies. There is extensive evidence for localisation of Kv1 subunits at many central synaptic terminals but few clues to their presynaptic function. We have used the calyx of Held to investigate the role of presynaptic Kv1 channels in the rat by selectively blocking Kv1.1 and Kv1.2 containing channels with dendrotoxin-K (DTX-K) and tityustoxin-Kalpha (TsTX-Kalpha) respectively. We show that Kv1.2 homomers are responsible for two-thirds of presynaptic low threshold current, whilst Kv1.1/Kv1.2 heteromers contribute the remaining current. These channels are located in the transition zone between the axon and synaptic terminal, contrasting with the high threshold K+ channel subunit Kv3.1 which is located on the synaptic terminal itself. Kv1 homomers were absent from bushy cell somata (from which the calyx axons arise); instead somatic low threshold channels consisted of heteromers containing Kv1.1, Kv1.2 and Kv1.6 subunits. Current-clamp recording from the calyx showed that each presynaptic action potential (AP) was followed by a depolarising after-potential (DAP) lasting around 50 ms. Kv1.1/Kv1.2 heteromers had little influence on terminal excitability, since DTX-K did not alter AP firing. However TsTX-Kalpha increased DAP amplitude, bringing the terminal closer to threshold for generating an additional AP. Paired pre- and postsynaptic recordings confirmed that this aberrant AP evoked an excitatory postsynaptic current (EPSC). We conclude that Kv1.2 channels have a general presynaptic function in suppressing terminal hyperexcitability during the depolarising after-potential.
authors.affiliation: Department of Cell Physiology and Pharmacology, University of Leicester, PO Box 138, Leicester LE1 9HN, UK.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Dodson
authors.forename: Brian
authors.initials: B
authors.lastname: Billups
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rusznák
authors.forename: Géza
authors.initials: G
authors.lastname: Szûcs
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Barker
authors.forename: Ian D
authors.initials: ID
authors.lastname: Forsythe
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004553:Electric Conductivity; D066298:In Vitro Techniques; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar
chemical_list: D051668:Delayed Rectifier Potassium Channels; C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel