Kinetics and functional consequences of BK Channels activation by N-type Ca2+ channels in the dendrite of mouse neocortical layer-5 pyramidal neurons (Blömer et al., 2024)

The back propagation of an action potential (AP) from the axon/soma to the dendrites plays a central role in dendritic integration. This process involves the intricate orchestration of various ion channels, yet a comprehensive understanding of the contribution of each channel type remains elusive. In this study, we leverage ultrafast membrane potential recordings (Vm) and Ca2+ imaging techniques to shed light on the involvement of N-type voltage-gated Ca2+ channels (VGCCs) in layer-5 neocortical pyramidal neurons' apical dendrites. Our findings reveal a selective interaction between N-type VGCCs and large-conductance Ca2+-activated K+ channels (BK CAKCs). Remarkably, we observe that BK CAKCs are activated within a mere 500 µs after the AP peak, preceding the peak of the Ca2+ current triggered by the AP. Consequently, when N-type VGCCs are inhibited, the early broadening of the AP shape amplifies the activity of other VGCCs, leading to an augmented total Ca2+ influx. Our NEURON model, constructed to replicate and support these experimental results, underscores the critical coupling between N-type and BK channels. This study not only redefines the conventional role of N-type VGCCs as primarily involved in presynaptic neurotransmitter release but also establishes their distinct and essential function as activators of BK CAKCs in neuronal dendrites. Furthermore, our results provide original functional validation of a physical interaction between Ca2+ and K+ channels, elucidated through ultrafast kinetic reconstruction. This insight enhances our understanding of the intricate mechanisms governing neuronal signaling and may have far-reaching implications in the field.

Model Type: Neuron or other electrically excitable cell

Region(s) or Organism(s): Neocortex

Cell Type(s): Neocortex L5/6 pyramidal GLU cell

Currents: I Calcium; I K; I K,Ca; I Na, slow inactivation; I Potassium; IK Bkca; IK Skca




Model Concept(s): Action Potentials; Active Dendrites; Dendritic Action Potentials

Simulation Environment: NEURON


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