Postnatal development of GABAB receptor-mediated modulation of voltage-activated Ca2+ currents in mouse brain-stem...

GABAB receptors modulate respiratory rhythm generation in adult mammals. However, little is currently known of their functional significance during postnatal development. In the present investigation, the effects of GABAB receptor activation on voltage-activated Ca2+ currents were examined in rhythmically active neurons of the pre-Bötzinger complex (PBC). Both low- (LVA) and high-voltage-activated (HVA) Ca2+ currents were present from the first postnatal day (P1). The density of LVA Ca2+ currents increased during the first week, whilst the density of HVA Ca2+ currents increased after the first week. In the second postnatal week, the HVA Ca2+ currents were composed of L- (47 +/- 10%) and N-type (21 +/- 8%) currents plus a 'residual' current, whilst there were no N-type currents detectable in the first few days. The GABAB receptor agonist baclofen (30 microM) increased LVA Ca2+ currents (30 +/- 11%) at P1-P3, but it decreased the currents (35 +/- 11%) at P7-P15 without changing its time course. At all ages, baclofen (30 microM) decreased the HVA Ca2+ currents by approximately 54%. Threshold of baclofen effects on both LVA and HVA Ca2+ currents was 5 microM at P1-P3 and lower than 1 microM at P7-P15. The effect of baclofen was abolished in the presence of the GABAB receptor antagonist CGP 55845A (50 nM). We conclude that both LVA and HVA Ca2+ currents increased postnatally. The GABAB receptor-mediated modulation of these currents undergo marked developmental changes during the first two postnatal weeks, which may contribute essentially to modulation of respiratory rhythm generation.