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J Neurophysiol (January 14, 2009). doi:10.1152/jn.91053.2008
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Submitted on September 19, 2008
Revised on December 18, 2008
Accepted on January 5, 2009

Participation of Kv1 channels in control of membrane excitability and burst generation in Mesencephalic V neurons

Chie-Fang Hsiao1, Gurvinder Kaur1, Angela Vong1, Harpreet Bawa1, and Scott H. Chandler1*

1 UCLA

* To whom correspondence should be addressed. E-mail: schandler{at}physci.ucla.edu.

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 brainstem slices (P8 P12) using whole cell current and voltage patch clamp methods. {alpha}-dendrotoxin application, a toxin with high specificity for Kv1.1, 1.2 and 1.6 channels, demonstrated the presence of a low threshold K+ current that activated rapidly around 50mV, and was relatively non inactivating over a one second period and had a V1/2max of -36.2mV. Other toxins, specific for individual channels containing either Kv 1.1, 1.2 or 1.3 {alpha}-subunits, were applied individually, or in combination, and demonstrated 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 {alpha}-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 {alpha}-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.







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