Kv1 channels selectively prevent dendritic hyperexcitability in rat Purkinje cells

Abstract

Purkinje cells, the sole output of the cerebellar cortex, encode the timing signals required for motor coordination in their firing rate and activity pattern. Dendrites of Purkinje cells express a high density of P/Q-type voltage-gated calcium channels and fire dendritic calcium spikes. Here we show that dendritic subthreshold Kv1.2 subunit-containing Kv1 potassium channels prevent generation of random spontaneous calcium spikes. With Kv1 channels blocked, dendritic calcium spikes drive bursts of somatic sodium spikes and prevent the cell from faithfully encoding motor timing signals. The selective dendritic function of Kv1 channels in Purkinje cells allows them to effectively suppress dendritic hyperexcitability without hindering the generation of somatic action potentials. Further, we show that Kv1 channels also contribute to dendritic integration of parallel fibre synaptic input. Kv1 channels are often targeted to soma and axon and the data presented support a major dendritic function for these channels.

Kv3.3 Channels at the Purkinje Cell Soma Are Necessary for Generation of the Classical Complex Spike Waveform

“…This result highlights the importance of Kv1 channels in shaping the complex spike, although block of Kv1 channels cannot account for the effects of TEA because DTX-K caused only minor changes in complex spike properties. Kv1 channels selectively regulate dendritic excitability of PCs (Khavandgar et al, 2005), and therefore this result highlights the importance of certain dendritic conductances in shaping the somatic complex spike waveform.…”

“…We found that blocking DTX-sensitive Kv1 channels, which are thought to be expressed in PC dendritic membranes and absent from somas (Southan and Robertson, 2000;Khavandgar et al, 2005) (but see McKay et al, 2005), dramatically compromised robust repetitive spikelet activity without affecting repolarization of the first spike (Fig. 2).…”

“…The stereotyped complex spike consists of a fast, prominent first spike followed by two to six smaller, high-frequency spikelets. PCs possess multiple intrinsic somatic and dendritic conductances that may interact with synaptic inputs to sculpt membrane voltage signals (Llinas and Sugimori, 1980a,b;Raman and Bean, 1997;Womack and Khodakhah, 2002;Swensen and Bean, 2003;McKay and Turner, 2004;Khavandgar et al, 2005). However, discrepancies remain regarding the ionic mechanisms responsible for the generation of the complex spike, including whether spikelets are generated at somatic or dendritic membranes and, more generally, the importance of somatic versus dendritic excitability to the somatic complex spike waveform (Callaway et al, 1995;Callaway and Ross, 1997;Hansel and Linden, 2000;Schmolesky et al, 2002;Weber et al, 2003;Davie and Hausser, 2004).…”

Postsynaptic Density-93 Clusters Kv1 Channels at Axon Initial Segments Independently of Caspr2

“…Therefore, as for Na v channels, it is likely that the AIS clustering of Kv1 channels is a multistep sequence of events, including directed trafficking to the axon followed by retention of channels at the AIS by PSD-93. Although we have focused on their AIS localization, Kv1 channels can also be detected along unmyelinated axons and in somatodendritic domains depending on the neuron (Trimmer and Rhodes, 2004;Khavandgar et al, 2005). Therefore, additional mechanisms regulating Kv1 channel localization in neurons remain to be identified.…”

The Linear Computational Algorithm of Cerebellar Purkinje Cells

“…It is noteworthy, however, that the contribution of active conductances can be remarkably balanced, allowing for linear summation of inputs, such as in CA1 pyramidal neurons (Cash and Yuste, 1999). We believe that the latter scenario also applies to Purkinje cells given their linear input-output function and the fact that blockade of subthreshold voltage-gated Kv1-type potassium channels significantly affects the amplitude and time course of somatic depolarizations evoked by a range of synaptic-like inputs (Khavandgar et al, 2005). The contribution of these channels is likely to be balanced by active conductances such as P/Q-type voltage-gated calcium channels, which are present at a high density in the dendrites of Purkinje cells (Usowicz et al, 1992).…”