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‐Kα (TsTX‐Kα) 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‐Kα 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.

Voltage-gated Potassium Channel (Kv) Subunits Expressed in the Rat Cochlear Nucleus

“…Kv, K 1 channel; LVA, low voltage-activated; HVA, high voltage-activated; VCN, ventral cochlear nucleus; DCN, dorsal cochlear nucleus. Dodson et al 2003;Pál et al 2004)], which is also indicated in Tables 2-4. Table 2 summarizes the results of experiments aimed at the detection of the dendrotoxin-sensitive LVA channel subunits.…”

“…Table 2 summarizes the results of experiments aimed at the detection of the dendrotoxin-sensitive LVA channel subunits. As seen, the expression of the Kv1.1 subunit has been well documented in several species and in various cell types, especially in the VCN (Sequier et al 1990;Wang et al 1994;Grigg et al 2000;Bal and Oertel 2001;Dodson et al 2003;Rosenberger et al 2003;Caminos et al 2005;Jung et al 2005;Pál et al 2005;Bortone et al 2006). In the DCN, however, the situation is somewhat less clear; although the general presence of Kv1.1 protein has been noted (Sequier et al 1990;Wang et al 1994), cell-specific labeling was reported in the bat only (Rosenberger et al 2003).…”

Molecular Targets for Antiepileptic Drug Development

“…The M-type current (mediated by K v 7.2-7.5) is proven as a target by the effect of retigabine and other channel openers in amygdala-kindled seizures. Presynaptic Atype K ϩ currents are also particularly significant, 427 because genetic defects in K v 1.1 in mice and humans are associated with partial or limbic seizures. 35,114 -116 The channels responsible for the A-type current would therefore appear to be promising targets.…”

Information processing in the axon

“…Several subtypes of voltage-gated potassium channels have been identified in myelinated and unmyelinated axons. K v 1.1, K v 1.2, K v 1.4, K v 3.1 and K v 3.4 have been identified in mammalian axons [6][7][8][9][10][11][12][13][14] . In addition, large-conductance calcium-dependent potassium channels (BK, also called Maxi-K or Slo1 channels) are present in axons and presynaptic terminals [15][16][17][18][19] .…”