Participation of Kv1 Channels in Control of Membrane Excitability and Burst Generation in Mesencephalic V Neurons

Abstract

The function and biophysical properties of low threshold Kv1 current in control of membrane resonance, subthreshold oscillations, and bursting in mesencephalic V neurons (Mes V) were examined in rat brain stem slices (P8–P12) using whole cell current and voltage patch-clamp methods. α-dendrotoxin application, a toxin with high specificity for Kv1.1, 1.2, and 1.6 channels, showed the presence of a low-threshold K+current that activated rapidly around −50 mV and was relatively noninactivating over a 1-s period and had a V1/2max of −36.2 mV. Other toxins, specific for individual channels containing either Kv 1.1, 1.2, or 1.3 α-subunits, were applied individually, or in combination, and showed that Kv1 channels are heteromeric, composed of combinations of subunits. In current-clamp mode, toxin application transformed the high-frequency resonant properties of the membrane into a low-pass filter and concomitantly reduced the frequency of the subthreshold membrane oscillations. During this period, rhythmical bursting was transformed into low-frequency tonic discharge. Interestingly, in a subset of neurons that did not show bursting, low doses of α-dendrotoxin (α-DTX) sufficient to block 50% of the low threshold Kv1 channels induced bursting and increased the resonant peak impedance and subthreshold oscillations, which was replicated with computer simulation. This suggests that a critical balance between inward and outward currents is necessary for bursting. This was replicated with computer simulation. Single cell RT-PCR and immunohistochemical methods confirmed the presence of Kv1.1, 1.2, and 1.6 α-subunits in Mes V neurons. These data indicate that low threshold Kv1 channels are responsible for membrane resonance, contribute to subthreshold oscillations, and are critical for burst generation.