Subthreshold inactivation of voltage-gated K+ channels modulates action potentials in neocortical bitufted...

Voltage-gated K+ channels perform many functions in integration of synaptic input and action potential (AP) generation. In this study we show that in bitufted interneurones from layer 2/3 of the somatosensory cortex, the height and width of APs recorded at the soma are sensitive to changes in the resting membrane potential, suggesting subthreshold activity of voltage-gated conductances. Attributes of K+ currents examined in nucleated patches revealed a fast subthreshold-inactivating K+ conductance (K(f)) and a slow suprathreshold-inactivating K+ conductance (K(s)). Simulations of these K+ conductances, incorporated into a Hodgkin-Huxley-type model, suggested that during a single AP or during low frequency trains of APs, subthreshold inactivation of K(f) was the primary modulator of AP shape, whereas during trains of APs the shape was governed to a larger degree by K(s) resulting in the generation of smaller and broader APs. Utilizing the facilitating function of unitary pyramidal-to-bitufted cell synaptic transmission, single back-propagating APs were initiated in a bitufted interneurone by repeated stimulation of a presynaptic pyramidal cell. Ca2+ imaging and dendritic whole-cell recordings revealed that modulation of APs, which also affect the shape of back-propagating APs, resulted in a change in dendritic Ca2+ influx. Compartmental simulation of the back-propagating AP suggested a mechanism for the modulation of the back-propagating AP height and width by subthreshold activation of K(f). We speculate that this signal may modulate retrograde GABA release and consequently depression of synaptic efficacy of excitatory input from neighbouring pyramidal neurones.