Differential distribution of voltage-gated ion channels in cortical neurons

Abstract

Neurons contain different functional somatodendritic and axonal domains, each with a characteristic distribution of voltage-gated ion channels, synaptic inputs, and function. The dendritic tree of a cortical pyramidal neuron has 2 distinct domains, the basal and the apical dendrites, both containing dendritic spines; the different domains of the axon are the axonal initial segment (AIS), axon proper (which in myelinated axons includes the node of Ranvier, paranodes, juxtaparanodes, and internodes), and the axon terminals. In the cerebral cortex, the dendritic spines of the pyramidal neurons receive most of the excitatory synapses; distinct populations of γ-aminobutyric acid (GABA)ergic interneurons target specific cellular domains and thus exert different influences on pyramidal neurons. The multiple synaptic inputs reaching the somatodendritic region and generating excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) sum and elicit changes in membrane potential at the AIS, the site of initiation of the action potential.

Selective attenuation of Ether-a-go-go related K+ currents by endogenous acetylcholine reduces spike-frequency adaptation and network correlation

“…In addition, the potential targets of mAChR modulation we examined are likely located within different compartments. ERG is expressed at high levels on dendrites (Hardman and Forsythe, 2009, Westenbroek, 2009) while M (KCNQ) channels are predominantly expressed on the cell body and the axons of the neocortical neurons and SK channel on dendritic spines (Trimmer, 2015, Child and Benarroch, 2014). These spatial differences may enable different subsets of cholinergic axons to selectively regulate different K + currents.…”

Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity

“…Accordingly, the molecular heterogeneity of axonal KChs, and the restricted subcompartmentalization of different isoforms within axons, is extensive (Table 1, Figure 1). Disruption of these defined patterns of subcellular localization is associated with a variety of neurological pathologies (Child and Benarroch, 2014), and axonal KChs have both established utility ( e.g. , retigabine, dalfampridine) and future potential (Judge et al, 2007) as drug targets.…”

“…Moreover, the KChs that are highly concentrated at the AIS are dynamically regulated to yield distinct local regulation of ion channel function (Bender and Trussell, 2012; Kole and Stuart, 2012). While this unique neuronal subcompartment makes up only a tiny fraction of the neuronal plasma membrane surface area, it is emerging as a “hot spot” for disease, with a preponderance of mutations associated with inherited epilepsies in genes encoding proteins, including KChs, selectively expressed at the AIS (Child and Benarroch, 2014; Wimmer et al, 2010). The localization of KChs and other AIS proteins is also altered in response to injury and disease, and in numerous neurological and psychiatric disorders (Buffington and Rasband, 2011; Buttermore et al, 2013),…”

Neuronal Calcium Imaging, Excitability, and Plasticity Changes in the Aldh2–/– Mouse Model of Sporadic Alzheimer’s Disease

“…Further, the location of the K Ca AHP channels is important to consider. K Ca channels, which are critical to neuronal repolarization and the AHP, have been mostly identified in the somatodendritic region of pyramidal neurons [88][89][90][91][92]. Thus, it is possible that recordings of mostly somatic potentials using the sharp electrode technique did not permit identification of synaptic changes in dendritic spines or finer processes negatively impacted in the Aldh2 -/model [55].…”