Postnatal development of GABA(B) receptor-mediated modulation of voltage-activated Ca2+ currents in mouse brain-stem neurons

GABA(B) 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 GABA(B) receptor activation on voltage-activated Ca2+ currents were examined in rh ythmically active neurons of the pre-Botzinger complex (PBC). Both low- (LV A) and high-voltage-activated (HVA) Ca2+ currents were present from the fir st postnatal day (P1). The density of LVA Ca2+ currents increased during th e first week, whilst the density of HVA Ca2+ currents increased after the f irst week. In the second postnatal week, the HVA Ca2+ currents were compose d of L- (47 +/- 10%) and N-type (21 +/- 8%) currents plus a 'residual' curr ent, whilst there were no N-type currents detectable in the first few days. The GABA(B) receptor agonist baclofen (30 mu M) increased LVA Ca2+ current s (30 +/- 11%) at P1-P3, but it decreased the currents (35 +/- 11%) at P7-P 15 without changing its time course. At all ages, baclofen (30 mu M) decrea sed the HVA Ca2+ currents by approximate to 54%. Threshold of baclofen effe cts on both LVA and HVA Ca2+ currents was 5 mu M at P1-P3 and lower than 1 mu M at P7-P15. The effect of baclofen was abolished in the presence of the GABA(B) receptor antagonist CGP 55845A (50 nM). We conclude that both LVA and HVA Ca2+ currents increased postnatally. The GABA(B) receptor-mediated modulation of these currents undergo marked developmental changes during th e first two postnatal weeks, which may contribute essentially to modulation of respiratory rhythm generation.