Kinetic Diversity of Single-Channel Burst Openings Underlying Persistent Na + Current in Entorhinal Cortex Neurons

Abstract

The kinetic diversity of burst openings responsible for the persistent Na + current ( I NaP) in entorhinal cortex neurons was examined by separately analyzing single bursts. Although remarkable kinetic variability was observed among bursts in terms of intraburst opening probability and mean open and closed times, the values of time constants describing intraburst open times ( τ o(b)s) and closed times ( τ c(b)s) were distributed around well-defined peaks. At −40 mV, τ o(b) peaks were found at ∼0.34 ( τ o(b)1) and 0.77 ( τ o(b)2) ms, and major τ c(b) peaks were found at ∼0.24 ( τ c(b)1) and 0.54 ( τ c(b)2) ms. In ∼80% of the bursts two preferential gating modes were found that consisted of a combination of either τ o(b)1 and τ c(b)2 (“intraburst mode 1”), or τ o(b)2 and τ c(b)1 (“intraburst mode 2”). Individual channels could switch between different gating modalities, but normally tended to maintain a specific gating mode for long periods. Mean burst duration also displayed considerable variability. At least three time constants were found to describe burst duration, and the frequencies at which each of the corresponding “bursting states” occurred varied in different channels. Short-lasting bursting states were preferentially associated with intraburst mode 1, whereas very-long-lasting bursts tended to gate according to mode 2 only or other modes that included considerably longer mean open times. These results show that I NaP channels can generate multiple intraburst open and closed states and bursting states, but these different kinetic states tend to combine in definite ways to produce a limited number of prevalent, well-defined gating modalities. Modulation of distinct gating modalities in individual Na + channels may be a powerful form of plasticity to influence neuronal excitability and function.