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

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.

Keywords: 4-Aminopyridine; I(A); Mice; Neocortex; Phrixotoxin-2; RuBi-glutamate.