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

Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 01/2009; 28(53):14329-40. DOI: 10.1523/JNEUROSCI.4833-08.2008
Source: PubMed


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.

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    • "By contrast , Punkinje cells does not express Kv1 . 1 subunits ( Khavandgar et al . , 2005 ; Lorincz and Nusser , 2008 ) . "
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    • "Although expression of Na v 1.1 in pyramidal neurons has been found, this is rare compared with its almost ubiquitous expression in interneurons. Unlike Na v 1.1 and Na v 1.2, Na v 1.6 shows a distal gradient of AIS expression in both pyramids and inhibitory neurons (Lorincz and Nusser, 2008). Figure 8 shows colabeling of AIS with antibodies against Na v b1, Na v 1.1, Na v 1.2, and Na v 1.6. "
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    • "Shaker (Kv1), Shab (Kv2) and KCNQ2/3 voltage-gated K + channels localized to the AIS regulate action potential threshold, duration and frequency (Rasband et al., 1998; Dodson et al., 2002; Pan et al., 2006; Goldberg et al., 2008; Johnston et al., 2008; Lorincz and Nusser, 2008; Sarmiere et al., 2008; Shah et al., 2008). The AIS ion channel complement is not fixed and can vary across neuronal cell types to facilitate distinct patterns of excitability (Lorincz and Nusser, 2008; Bender and Trussell, 2012). "
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