Resilient RTN Fast Spiking in Kv3.1 Null Mice Suggests Redundancy in the Action Potential Repolarization Mechanism

J Neurophysiol. 2002 Mar;87(3):1303-10. doi: 10.1152/jn.00556.2001.

Abstract

Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K(+) channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23 degrees C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1(-/-)) compared with their wild-type (Kv3.1(+/+)) counterparts had reduced amplitudes (-6%) and fast after-hyperpolarizations (-16%). At 34 degrees C, action potentials in Kv3.1(-/-) mice had increased duration (21%) due to a reduced rate of repolarization (-30%) when compared with wild-type controls. Action potential trains in Kv3.1(-/-) were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship (F/I) at 34 degrees C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca(2+) bursts in Kv3.1(-/-) RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Behavior, Animal
  • Intralaminar Thalamic Nuclei / cytology
  • Intralaminar Thalamic Nuclei / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / physiology
  • Neuropeptides / genetics*
  • Neuropeptides / metabolism
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Shaw Potassium Channels

Substances

  • Neuropeptides
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Shaw Potassium Channels