Interaction between Duration of Activity and Time Course of Recovery from Slow Inactivation in Mammalian Brain Na+Channels

Abstract

NaII and NaIIA channels are the most abundant voltage-gated channels in neonatal and adult cortex, respectively. The relationships between activity and availability for activation of these channels were examined using the Xenopus expression system. The main point of this work is that the time constant (τ) of recovery from the unavailable (inactivated) pool is related to the duration (t) of previous activation by a power law: τ(t) =p·t D, with a scaling power D congruent to 0.8 and 0.5 for NaII and NaIIA, respectively, and p as a constant kinetic setpoint. These relationships extend from tens of milliseconds to several minutes and are intrinsic to the channel protein. Coexpression of β1 auxiliary subunit, together with the α subunit of the NaIIA channel, modulates the constant kinetic setpoint but not the scaling power of the latter. The power law scaling between activity and availability is not a universal property of ion channels; unlike that of voltage-gated sodium channels, the rate of recovery from slow inactivation of the ShakerB channel is virtually insensitive to the duration of previous stimuli. It is suggested that the power law scaling described here can act as a molecular memory mechanism that preserves traces of previous activity, over a wide range of time scales, in the form of modulated reaction rates. This mechanism should be considered when theorizing about the dynamics of threshold and firing patterns of neurons.