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The Journal of Neuroscience, December 31, 2008, 28(53):14329-14340; doi:10.1523/JNEUROSCI.4833-08.2008

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Cellular/Molecular
Cell-Type-Dependent Molecular Composition of the Axon Initial Segment

Andrea Lorincz and Zoltan Nusser

Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary

Correspondence should be addressed to either of the following: Andrea Lorincz or Zoltan Nusser, Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony Street 43, 1083 Budapest, Hungary, Email: lorincz{at}koki.hu or Email: nusser{at}koki.hu

The exact site of initiation and shape of action potentials vary among different neuronal types. The reason for this variability is largely unknown, but the subunit composition, density and distribution of voltage-gated sodium (Nav) and potassium (Kv) channels within the axon initial segment (AIS) are likely to play a key role. Here, we asked how heterogeneous are the density and distribution of Nav and Kv channels within the AISs of a variety of excitatory and inhibitory neurons. Most of the studied cell types expressed a high density of Nav1.6, Kv1.1, and Kv1.2 subunits in their AIS, but the Nav1.1 subunit could only be detected in GABAergic interneurons. A proximo-distal gradient in the density of these subunits was observed within the AIS of certain nerve cells but not in others. For example, a gradual increase of the Nav1.6 subunit was observed in cortical layer 2/3 and hippocampal CA1 pyramidal cell (PC) AISs, whereas its density was rather uniform in layer 5 PC AISs. The Nav1.1 subunit was distributed evenly along the AIS of short-axon cells of the main olfactory bulb but was restricted to the proximal part of the AIS in cortical and cerebellar interneurons. Our results reveal a cell type-dependent expression of sodium and potassium channel subunits with varying densities along the proximo-distal axis of the AISs. This precise arrangement is likely to contribute to the diversity of firing properties observed among central neurons.

Key words: voltage-gated ion channels; immunohistochemistry; axon initial segment; cortex; hippocampus; cerebellum; olfactory bulb

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Received Oct. 8, 2008; revised Nov. 11, 2008; accepted Nov. 13, 2008.

Correspondence should be addressed to either of the following: Andrea Lorincz or Zoltan Nusser, Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony Street 43, 1083 Budapest, Hungary, Email: lorincz{at}koki.hu or Email: nusser{at}koki.hu

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