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A-type K(+) channels impede supralinear summation of clustered glutamatergic inputs in layer 3 neocortical pyramidal neurons

Biro, AA; Bremaud, A; Falck, J; Ruiz, AJ; (2018) A-type K(+) channels impede supralinear summation of clustered glutamatergic inputs in layer 3 neocortical pyramidal neurons. Neuropharmacology , 140 pp. 86-99. 10.1016/j.neuropharm.2018.07.005. Green open access

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Abstract

A-type K+ channels restrain the spread of incoming signals in tufted and apical dendrites of pyramidal neurons resulting in strong compartmentalization. However, the exact subunit composition and functional significance of K+ channels expressed in small diameter proximal dendrites remain poorly understood. We focus on A-type K+ channels expressed in basal and oblique dendrites of cortical layer 3 pyramidal neurons, in ex vivo brain slices from young adult mice. Blocking putative Kv4 subunits with phrixotoxin-2 enhances depolarizing potentials elicited by uncaging RuBi-glutamate at single dendritic spines. A concentration of 4-aminopyridine reported to block Kv1 has no effect on such responses. 4-aminopyridine and phrixotoxin-2 increase supralinear summation of glutamatergic potentials evoked by synchronous activation of clustered spines. The effect of 4-aminopyridine on glutamate responses is simulated in a computational model where the dendritic A-type conductance is distributed homogeneously or in a linear density gradient. Thus, putative Kv4-containing channels depress excitatory inputs at single synapses. The additional recruitment of Kv1 subunits might require the synchronous activation of multiple inputs to regulate the gain of signal integration.

Type: Article
Title: A-type K(+) channels impede supralinear summation of clustered glutamatergic inputs in layer 3 neocortical pyramidal neurons
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuropharm.2018.07.005
Publisher version: https://doi.org/10.1016/j.neuropharm.2018.07.005
Language: English
Additional information: Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).
Keywords: IA; mice; neocortex; RuBi-glutamate; phrixotoxin-2; 4-aminopyridine
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10052543
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