Neuronal expression of the intermediate conductance calcium-activated potassium channel KCa3.1 in the mammalian central nervous system.

The expression pattern and functional roles for calcium-activated potassium channels of the KCa2.x family and KCa1.1 have been extensively examined in central neurons. Recent work indicates that intermediate conductance calcium-activated potassium channels (KCa3.1) are also expressed in central neurons of the cerebellum and spinal cord. The current study used immunocytochemistry and GFP linked to KCNN4 promoter activity in a transgenic mouse to determine the expression pattern of KCa3.1 channels in rat or mouse neocortex, hippocampus, thalamus, and cerebellum. KCa3.1 immunolabel and GFP expression were closely matched and detected in both excitatory and inhibitory cells of all regions examined. KCa3.1 immunolabel was localized primarily to the somatic region of excitatory cells in cortical structures but at the soma and over longer segments of dendrites of cells in deep cerebellar nuclei. More extensive labeling was apparent for inhibitory cells at the somatic and dendritic level with no detectable label associated with axon tracts or regions of intense synaptic innervation. The data indicate that KCa3.1 channels are expressed in the CNS with a differential pattern of distribution between cells, suggesting important functional roles for these calcium-activated potassium channels in regulating the excitability of central neurons.

Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells.

Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca(2+)-activated K(+) channels are known to control spike frequency in central neurons, Ca(2+)-activated K(+) channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca(2+) channels at the nanodomain level to support a previously undescribed transient voltage- and Ca(2+)-dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca(2+) influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input.