%0 Journal Article
%T The Kv2.1 K+ channel targets to the axon initial segment of hippocampal and cortical neurons in culture and in situ
%A Patrick D Sarmiere
%A Cecile M Weigle
%A Michael M Tamkun
%J BMC Neuroscience
%D 2008
%I BioMed Central
%R 10.1186/1471-2202-9-112
%X Transfected and endogenous Kv2.1 is now demonstrated to preferentially accumulate within the axon initial segment (AIS) over other neurite processes; 87% of 14 DIV hippocampal neurons show endogenous channel concentrated at the AIS relative to the soma and proximal dendrites. In contrast to the localization observed in pyramidal cells, GAD positive inhibitory neurons within the hippocampal cultures did not show AIS targeting. Photoactivable-GFP-Kv2.1-containing clusters at the AIS were stable, moving <1 ¦Ìm/hr with no channel turnover. Photobleach studies indicated individual channels within the cluster perimeter were highly mobile (FRAP ¦Ó = 10.4 ¡À 4.8 sec), supporting our model that Kv2.1 clusters are formed by the retention of mobile channels behind a diffusion-limiting perimeter. Demonstrating that the AIS targeting is not a tissue culture artifact, Kv2.1 was found in axon initial segments within both the adult rat hippocampal CA1, CA2, and CA3 layers and cortex.In summary, Kv2.1 is associated with the axon initial segment both in vitro and in vivo where it may modulate action potential frequency and back propagation. Since transfected Kv2.1 initially localizes to the AIS before appearing on the soma, it is likely multiple mechanisms regulate Kv2.1 trafficking to the cell surface.Voltage-gated ion channels are often highly localized in electrically excitable cells such as nerve and muscle. As originally noted by Trimmer and colleagues [1], the Kv2.1 delayed rectifier is expressed primarily in the somatic region of hippocampal neurons where it is found in cell surface clusters that can co-localize with ryanodine receptors and SR-like subsurface cisterns [2,3]. Interestingly, these clusters also co-localize with cholinergic synapses in spinal motor neurons [4]. Kv2.1 represents the predominant delayed rectifier current in hippocampal neurons where its activity and localization are highly regulated [5,6]. Glutamate or carbachol treatments induce both Kv2.1 dephosphor
%U http://www.biomedcentral.com/1471-2202/9/112