engleski

BICUCULLINE SENSITIVE GAIN MODULATION MECHANISM IN RESPIRATORY PREMOTOR NEURONS

Introduction: A possible mechanism underlying adaptive control of the respiratory system is gain modulation of the discharge frequency (Fn) patterns of medullary respiratory neurons. This mechanism may be mediated by GABAA receptors. The aim of this study was to test whether the antagonism of GABAA receptors results in an Fn pattern that is an amplified replica of the underlying control pattern. Materials and methods: Multibarrel micropipettes were used in halothane anesthetized, paralyzed, ventilated, vagotomized dogs to record single unit activity from inspiratory and expiratory neurons in the caudal ventral respiratory group and to picoeject GABAA receptor antagonists bicuculline and picrotoxinin. The moving time average of phrenic nerve activity was used to determine respiratory phase durations and to synchronize cycle-triggered histograms of discharge patterns. Results: Picoejections of bicuculline and picrotoxinin had qualitatively different effects on the discharge patterns of respiratory neurons. Bicuculline caused an increase in the discharge rate during the neuron's active phase without inducing activity during the neuron's normally silent phase. The resulting discharge patterns were amplified replicas (x2-3) of the underlying preejection phasic patterns. In contrast, picoejection of picrotoxinin did not increase the peak discharge rate during the neuron's active phase but induced a tonic level of activity during the neuron's normally silent phase. The maximum effective bicuculline dose (15 +/- 1.8 pmol/min) was considerably smaller than that for picrotoxinin (280 +/- 53 pmol/min). Conclusion: These findings suggest that GABAA receptors with differential pharmacology mediate distinct functions within the same neuron, a) gain modulation that is bicuculline sensitive but picrotoxinin insensitive and b) silent-phase inhibition blocked by picrotoxinin. These studies also suggest that the choice of an antagonist is an important consideration in the determination of GABA receptor function within the respiratory motor control system.

GABA receptors; bicuculline; gain modulation; respiratory neurons

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