GABA-A RECEPTOR MEDIATED FAST SYNAPTIC INHIBITION IN THE RABBIT BRAIN-STEM RESPIRATORY SYSTEM

The involvement of GABA mediated neurotransmission in the central control of respiration was investigated by administration of the specific GABA(A) receptor agonist muscimol and the specific GABA(A) receptor antagonist bicuculline into the fourth cerebral ventricle of the rabbit. Cycle-triggered averaging of the phrenic nerve activity (PNA) was used to quantify drug-induced changes of the central respiratory pattern. Muscimol reduced the peak amplitude of PNA and increased the duration of the respiratory phases. High amounts of muscimol led to a long-lasting but reversible central apnea. Bicuculline very effectively blocked the effects of externally applied muscimol. Blockade of intrinsically active GABAergic neurotransmission by bicuculline resulted in a multitude of effects. Peak amplitude of PNA increased whereas the duration of both inspiration and expiration decreased. In this respect, effects of bicuculline and muscimol were complementary. Bicuculline reduced the slope of the inspiratory ramp, increased postinspiratory activity and induced an augmenting type of discharge activity in the last part of expiration resulting in a smooth transition between expiration and inspiration. In some cases the respiratory modulation was completely lost and PNA became perfectly tonic. This 'apneustic' type of respiratory pattern could be transformed into rhythmic breathing by increasing the respiratory drive. We conclude that neurotransmission via GABA(A) receptors is important for the maintenance of respiratory rhythm as well as the generation of normal respiratory pattern.