Presynaptic Kv1

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 Kv1.1/1.2 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 + channels Kv3.1, which are 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 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. 2 Voltage-gated K + conductances play multiple roles in regulating neuronal excitability. High threshold channels (such as Kv3) shape the action potential waveform and facilitate rapid repolarisation (Rudy & McBain, 2001). Low threshold K + channels which activate close to resting potentials (such as Kv1) regulate firing threshold and excitability (Brew & Forsythe, 1995) and their mutation or deletion may result in epilepsy and ataxia (Smart et al., 1998). Six of the seven Shaker-related Kv1 family members (Kv1.1-1.6) are expressed throughout the mammalian brain and there is extensive evidence for Kv1 localisation adjacent to nodes of Ranvier and at many central synaptic terminals (Wang et al., 1994). Owing to the difficulties in directly recording from nerve terminals, the function of presynaptic Kv1 channels remains elusive. Blockade of channels containing Kv1.1, Kv1.2 or Kv1.6 subunits by dendrotoxin-I caused spontaneous firing at the neuromuscular junction (Anderson & Harvey, 1988). Similar observations have been made at central synapses such as inhibitory cerebellar basket cell terminals where blockade of channels containing Kv1.1 and Kv1.2 subunits increased the rate and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) (Southan & sensitivity of these sIPSCs to tetrodotoxin and the absence of a rise in presynaptic [Ca 2+ ] i (Tan & Llano, 1999), suggest that the firing rate in basket cell terminals was increased rather than APs …