Axo-Somatic and Apical Dendritic Kv7/M Channels Differentially Regulate the Intrinsic Excitability of Adult Rat CA1 Pyramidal Cells

Abstract

Kv7/KCNQ/M channel subunits are widely expressed in peripheral and central neurons, where they give rise to a muscarinic-sensitive, subthreshold, and noninactivating K⁺ current (M current). Immunohistochemical data suggest that Kv7/M channels are expressed in both axons, somata and dendrites, but their distinctive roles in these compartments are not known. Here we used intracellular microelectrode recordings to monitor the effects of selective Kv7/M channel modulators focally applied to the axo-somatic region and to the apical dendrites of adult rat CA1 pyramidal cells. We show that both compartments express functional Kv7/M channels that synergistically control intrinsic neuronal excitability, albeit in different ways. Axo-somatic Kv7/M channels activate during the spike afterdepolarization (ADP) and counteract the depolarizing drive furnished by conjointly activated persistent Na⁺ channels. Thereby they limit the size and duration of the spike ADP and prevent its escalation into a somatic spike burst. Apical dendritic Kv7/M channels do not ordinarily regulate the somatic spike ADP and spike output. In hyperexcitable conditions that promote Ca²⁺ electrogenesis in these dendrites, they elevate the threshold for initiating Ca²⁺ spikes and associated downstream spike bursts. Thus the concerted activity of Kv7/M channels in both compartments serves to reduce the propensity to generate self-sustained burst responses and fosters a regular, stimulus-graded spike output of the neuron. Given that the activity of Kv7/M channels is regulated by multiple neurotransmitters, they may provide a substrate for neuromodulation of neuronal input/output relations at both the axo-somatic and apical dendritic regions.