Heteromeric Kv7.2/7.3 Channels Differentially Regulate Action Potential Initiation and Conduction in Neocortical Myelinated Axons

摘要: Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example the tight colocalization Kv7 potassium sodium (Nav) in axonal initial segment nodes Ranvier. The local biophysical properties these functional impact with Nav remain poorly understood. Here, we quantitatively examined myelinated rat neocortical pyramidal neurons using high-resolution confocal imaging patch-clamp recording. Kv7.2 7.3 immunoreactivity steeply increased within distal two-thirds axon was mirrored by conductance density estimates, which from ∼12 (proximal) to 150 pS μm−2 (distal). nodal M-currents were similar voltage dependence kinetics, carried Kv7.2/7.3 heterotetramers, 4% activated at resting membrane potential rapidly single-exponential time constants (∼15 ms 28 mV). Experiments computational modeling showed that while somatodendritic are strongly backpropagating action attenuate afterdepolarization repetitive firing, minimally recruited forward-propagating potential. Instead, domains found increase channel availability amplitude stabilizing Thus, clustering near serves specific context-dependent roles, both restraining initiation enhancing conduction