Dynamic activation of KATP channels in rhythmically active neurons

Authors


Abstract

  • 1The respiratory centre within the brainstem is one of the most active neuronal networks that generates ongoing rhythmic activity. Stabilization of such vital activity requires efficient processes for activity-correlated adjustment of neuronal excitability. Recent investigations have shown that a regulatory factor coupling electrical activity with cell metabolism comprises ATP-dependent K+ channels (KATP channels), which continuously adjust the excitability of respiratory neurons during normoxia and increasingly during hypoxia.
  • 2We used the single-cell antisense RNA amplification-polymerase chain reaction (PCR) technique to demonstrate that respiratory neurons co-express the sulphonylurea receptor SUR1 with the Kir6.2 potassium channel protein.
  • 3Single channel measurements on rhythmically active inspiratory neurons of the brainstem slice preparation of newborn mice revealed that KATP channels are periodically activated in synchrony with each respiratory cycle.
  • 4The Na+-K+-ATPase was inhibited with ouabain to demonstrate that oscillations of the channel open probability disappear, although respiratory activity persists for a longer time. Such findings indicate that KATP channel open probability reflects activity-dependent fluctuations in the ATP concentration within submembrane domains.
  • 5We also examined the effects of extracellular [K+] and hypoxia. All changes in the respiratory rhythm (i.e. changes in cycle length and burst durations) affected the periodic fluctuations of KATP channel activity.
  • 6The data indicate that KATP channels continuously modulate central respiratory neurons and contribute to periodic adjustment of neuronal excitability. Such dynamic adjustment of channel activity operates over a high range of metabolic demands, starting below physiological conditions and extending into pathological situations of energy depletion.

Ancillary