Activity-independent coregulation of IA and Ih in rhythmically active neurons

J Neurophysiol. 2005 Nov;94(5):3601-17. doi: 10.1152/jn.00281.2005. Epub 2005 Jul 27.

Abstract

The fast transient potassium or A current (IA) plays an important role in determining the activity of central pattern generator neurons. We have previously shown that the shal K+ channel gene encodes IA in neurons of the pyloric network in the spiny lobster. To further study how IA shapes pyloric neuron and network activity, we microinjected RNA for a shal-GFP fusion protein into four identified pyloric neuron types. Neurons expressing shal-GFP had a constant increase in IA amplitude, regardless of cell type. This increase in IA was paralleled by a concomitant increase in the hyperpolarization-activated cation current Ih in all pyloric neurons. Despite significant increases in these currents, only modest changes in cell firing properties were observed. We used models to test two hypotheses to explain this failure to change firing properties. First, this may reflect the mislocalization of the expressed shal protein solely to the somata and initial neurites of injected neurons, rendering it electrically remote from the integrating region in the neuropil. To test this hypothesis, we generated a multicompartment model where increases in IA could be localized to the soma, initial neurite, or neuropil/axon compartments. Although spike activity was somewhat more sensitive to increases in neuropil/axon versus somatic/primary neurite IA, increases in IA limited to the soma and primary neurite still evoked much more dramatic changes than were seen in the shal-GFP-injected neurons. Second, the effect of the increased IA could be compensated by the endogenous increase in Ih. To test this, we modeled the compensatory increases of IA and Ih with a cycling two-cell model. We found that the increase in Ih was sufficient to compensate the effects of increased IA, provided that they increase in a constant ratio, as we observed experimentally in both shal-injected and noninjected neurons. Thus an activity-independent homeostatic mechanism maintains constant neuronal activity in the face of dramatic increases in IA.

Publication types

  • Evaluation Study

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Biological Clocks / physiology*
  • Cells, Cultured
  • Computer Simulation
  • Feedback / physiology
  • Ion Channel Gating / physiology
  • Models, Neurological*
  • Motor Neurons / physiology*
  • Nerve Net / physiology*
  • Palinuridae
  • Potassium / metabolism*
  • Potassium Channels / physiology*
  • Pylorus / physiology

Substances

  • Potassium Channels
  • Potassium