Low threshold K⁺ currents (I_LT) activate near to resting potentials and influence action potential (AP) firing patterns. In the medial nucleus of the trapezoid body (MNTB) I_LT ensures generation of a single AP during each EPSC and is blocked by dendrotoxin-I (Brew & Forsythe, 1995), suggesting mediation by Kv1.1, Kv1.2 and/or Kv1.6 subunits. Here we investigate the subunit composition and function of pre- and postsynaptic low threshold K⁺ currents.

Immunohistochemistry showed that Kv1.1, Kv1.2 and Kv1.6 were expressed in the MNTB, but Kv1.4 and Kv1.5 were not. Brainstem slices (100Ð150 mm thick) were prepared from Lister Hooded rats (P6Ð14) humanely killed by decapitation. Subunit-specific toxins (100 nM) were applied during whole-cell patch recordings to investigate the contribution of Kv1 subunits to I_LT. DTX-K, a specific blocker of channels containing Kv1.1, blocked 90 ± 4 % of I_LT (n = 4, mean ± S.E.M.), whereas tityustoxin-Kα (TsTX), which blocks channels containing Kv1.2, blocked 48 ± 4 % of I_LT (n = 7). Thus I_LT is composed of two components: one is TsTX sensitive (hence I_LTS) and the other is TsTX resistant (I_LTR). The pharmacology and histology are consistent with I_LTS being mediated by Kv1.1/1.2 heteromers and I_LTR by Kv1.1/1.6 heteromers. Block of I_LTS caused trains of APs on depolarisation in current clamp, suggesting that I_LTS is dominant in maintaining the phenotypic single AP response of MNTB neurones. One explanation for this dominance is that I_LTS is preferentially located at a spike initiation region in the axon. Indeed Kv1.1 and Kv1.2 (I_LTS) immunoreactivity was concentrated in the initial 20Ð30 mm of the axon, whereas Kv1.6 (I_LTR) could not be detected axonally (n = 3).

We also examined the presynaptic low threshold K⁺ currents by making whole-cell recordings from the calyx. In contrast to the postsynaptic currents, TsTX blocked 87 ± 5 % of the presynaptic low threshold current (n = 7) and increased the number of action potentials fired, whereas DTX-K had no effect.

Low threshold K⁺ currents in MNTB neurones are mediated by two heteromeric Kv1 channels: I_LTS channels are Kv1.1/1.2 heteromers, whereas those of I_LTR are likely to be Kv1.1/1.6 heteromers. I_LTS has the dominant function in maintaining the single AP response, a property that may be conferred by its preferential localisation to the initial 20Ð30 mm of the axon. Presynaptic low threshold K⁺ channels have a different subunit composition to postsynaptic channels, with presynaptic AP firing being governed by channels containing Kv1.2 but not Kv1.1.

This work was supported by The Wellcome Trust.

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