Developmental changes in the modulation of respiratory rhythm generation by extracellular K+ in the isolated bullfrog brainstem

This study tested the hypothesis that voltage-dependent, respiratory-related activity in vitro, inferred from changes in [K(+)](o), changes during development in the amphibian brainstem. Respiratory-related neural activity was recorded from cranial nerve roots in isolated brainstem-spinal cord preparations from 7 premetamorphic tadpoles and 10 adults. Changes in fictive gill/lung activity in tadpoles and buccal/lung activity in adults were examined during superfusion with artificial CSF (aCSF) with [K(+)](o) ranging from 1 to 12 mM (4 mM control). In tadpoles, both fictive gill burst frequency (f(gill)) and lung burst frequency (f(lung)) were significantly dependent upon [K(+)](o) (r(2) > 0.75; p < 0.001) from 1 to 10 mM K(+), and there was a strong correlation between f(gill) and f(lung) (r(2) = 0.65; p < 0.001). When [K(+)](o) was raised to 12 mM, there was a reversible abolition of fictive breathing. In adults, fictive buccal frequency (f(buccal)), was significantly dependent on [K(+)](o) (r(2) = 0.47; p < 0.001), but [K(+)](o) had no effect on f(lung) (p > 0.2), and there was no significant correlation between f(buccal) and f(lung). These data suggest that the neural networks driving gill and lung burst activity in tadpoles may be strongly voltage modulated. In adults, buccal activity, the proposed remnant of gill ventilation in adults, also appears to be voltage dependent, but is not correlated with lung burst activity. These results suggest that lung burst activity in amphibians may shift from a "voltage-dependent" state to a "voltage-independent" state during development. This is consistent with the hypothesis that the fundamental mechanisms generating respiratory rhythm in the amphibian brainstem change during development. We hypothesize that lung respiratory rhythm generation in amphibians undergoes a developmental change from a pacemaker to network-driven process.