Abstract
Large conductance calcium-activated potassium channels (or BK channels) fulfil a multitude of roles in the central nervous system. At the soma of many neuronal cell types they control the speed of action potential (AP) repolarization and therefore they can have an impact on neuronal excitability. Due to their presence in nerve terminals they also regulate transmitter release. BK channels have also been shown to be present in the dendrites of some neurons where they can regulate the magnitude and duration of dendritic spikes. Here, we investigate the impact of modulating the activation of BK channels at different locations on the cellular excitability of cortical layer 5 pyramidal neurons. We find that while somatic BK channels help to repolarize APs at the soma and mediate the fast after-hyperpolarization, dendritic BK channels are responsible for repolarization of dendritic calcium spikes and thereby regulate somatic AP burst firing. We found no evidence for a role of dendritic BK channels in the regulation of backpropagating AP amplitude or duration. These experiments highlight the diverse roles of BK channels in regulating neuronal excitability and indicate that their functional impact depends on their subcellular location.
Highlights
Layer 5 (L5) pyramidal neurons are the primary output neurons in the cortex and play a key role in cortical signal processing
To directly test the role of BK channels at different locations on the regulation of neuronal excitability, we locally applied BK blockers to somatic and dendritic compartments allowing us to investigate the impact of BK channels at different locations in isolation. These experiments showed that in L5 pyramidal neurons somatic/axonal BK channels regulate action potential (AP) repolarization, whereas dendritic BK channels regulate the duration of dendritic calcium spikes, indicating that the functional impact of BK channels depends on their subcellular location
By locally blocking BK channels we show that somatic BK channels regulate AP duration, whereas dendritic BK channels regulate the duration of dendritic calcium spikes and thereby AP burst firing
Summary
Layer 5 (L5) pyramidal neurons are the primary output neurons in the cortex and play a key role in cortical signal processing. The basal-somatic region, which mainly receives thalamo-coritcal bottom-up inputs that have a rather direct impact on AP output, and a distal apical region that receives mostly top-down inputs from other cortical areas and generates dendritic calcium spikes promoting AP burst firing at the soma (Schiller et al, 1997; Larkum et al, 1999a,b; Williams and Stuart, 2002). These two regions of L5 pyramidal neurons do not integrate signals independently from each other. Somatic APs actively propagate into the apical dendrites of L5 neurons (Stuart and Sakmann, 1994) and the membrane potential at proximal apical dendritic locations determines the efficacy of forward propagation
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