Dynamic activation of K-ATP channels in rhythmically active neurons

1.The respiratory centre within the brainstem is one of the most active neu ronal networks that generates ongoing rhythmic activity. Stabilization of s uch vital activity requires efficient processes for activity-correlated adj ustment of neuronal excitability. Recent, investigations have shown that a regulatory factor coupling electrical activity with cell metabolism compris es ATP-dependent K+ channels (K-ATP channels), which continuously adjust th e excitability of respiratory neurons during normoxia and increasingly duri ng hypoxia. 2. We used the single-cell antisense RNA amplification-polymerase chain rea ction (PCR) technique to demonstrate that respiratory neurons co-express th e sulphonylurea receptor SUR1 with the Kir6.2 potassium channel protein. 3. Single channel measurements on rhythmically active inspiratory neurons o f the brainstem slice preparation of newborn mice revealed that K-ATP chann els are periodically activated in synchrony with each respiratory cycle. 4. The Na+-K+-ATPase was inhibited with ouabain to demonstrate that oscilla tions of the channel open probability disappear, although respiratory activ ity persists for a longer time. Such findings indicate that K-ATP channel o pen probability reflects activity-dependent fluctuations in the ATP concent ration within submembrane domains. 5. We also examined the effects of extracellular [K+] and hypoxia. All chan ges in the respiratory rhythm (i.e. changes in cycle length and burst durat ions) affected the periodic fluctuations of K-ATP. channel activity. 6. The data indicate that K-ATP channels continuously modulate central resp iratory neurons and contribute to periodic adjustment of neuronal excitabil ity. Such dynamic adjustment of channel activity operates over a high range of metabolic demands, starting below physiological conditions and extendin g into pathological situations of energy depletion.