Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea-pig neocortical neurones in slices

J Physiol. 1996 May 15;493 ( Pt 1)(Pt 1):83-97. doi: 10.1113/jphysiol.1996.sp021366.


1. Spike adaptation of neocortical pyramidal neurones was studied with sharp electrode recordings in slices of guinea-pig parietal cortex and whole-cell patch recordings of mouse somatosensory cortex. Repetitive intracellular stimulation with 1 s depolarizing pulses delivered at intervals of < 5 s caused slow, cumulative adaptation of spike firing, which was not associated with a change in resting conductance, and which persisted when Co2+ replaced Ca2+ in the bathing medium. 2. Development of slow cumulative adaptation was associated with a gradual decrease in maximal rates of rise of action potentials, a slowing in the post-spike depolarization towards threshold, and a positive shift in the threshold voltage for the next spike in the train; maximal spike repolarization rates and after-hyperpolarizations were unchanged. 3. The data suggested that slow adaptation reflects use-dependent removal of Na+ channels from the available pool by an inactivation process which is much slower than fast, Hodgkin-Huxley-type inactivation. 4. We therefore studied the properties of Na+ channels in layer II-III mouse neocortical cells using the cell-attached configuration of the patch-in-slice technique. These had a slope conductance of 18 +/- 1 pS and an extrapolated reversal potential of 127 +/- 6 mV above resting potential (Vr) (mean +/- S.E.M.; n = 5). Vr was estimated at -72 +/- 3 mV (n = 8), based on the voltage dependence of the steady-state inactivation (h infinity) curve. 5. Slow inactivation (SI) of Na+ channels had a mono-exponential onset with tau on between 0.86 and 2.33 s (n = 3). Steady-state SI was half-maximal at -43.8 mV and had a slope of 14.4 mV (e-fold)-1. Recovery from a 2 s conditioning pulse was bi-exponential and voltage dependent; the slow time constant ranged between 0.45 and 2.5 s at voltages between-128 and -68 mV. 6. The experimentally determined parameters of SI were adequate to simulate slow cumulative adaptation of spike firing in a single-compartment computer model. 7. Persistent Na+ current, which was recorded in whole-cell configuration during slow voltage ramps (35 mV s-1), also underwent pronounced SI, which was apparent when the ramp was preceded by a prolonged depolarizing pulse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Computer Simulation
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Kinetics
  • Male
  • Mice
  • Microelectrodes
  • Patch-Clamp Techniques
  • Pyramidal Cells / metabolism*
  • Sodium / metabolism*
  • Sodium Channel Blockers


  • Sodium Channel Blockers
  • Sodium