Agonist-specific maturation of GIRK current responses in acutely isolated pyramidal neurons of rat neocortex.

We performed whole-cell recordings from acutely isolated pyramidal cell somata of rat neocortex to measure and compare G protein-activated, inwardly rectifying K+ (GIRK) currents induced by adenosine, serotonin and baclofen at different postnatal stages (postnatal days 3-19). In about two thirds of neurons, baclofen-induced GIRK currents were already detected at postnatal days 3 and 4 (P3-P4) and almost all neurons between P5 and P19 were responsive. This robust response suggests that postsynaptic effects of baclofen occur much earlier than previously thought. Sensitivity to adenosine was around 70% during the first two postnatal weeks. Given the late maturation of functional synaptic inhibition in neocortex, we propose that phasic and/or tonic activation of GIRK current by baclofen and adenosine might serve as a mechanism to control neuronal excitability during early postnatal development. In marked contrast to the pronounced early sensitivity to baclofen and adenosine, only 20% of the neurons displayed a GIRK current response to serotonin during the first postnatal week. After that, about half of the neurons tested positive for serotonin. GIRK current densities for baclofen and adenosine attained a maximum at the end of the second postnatal week, whereas the serotonin-induced current showed a linear increase during the second and third week of life. Set in relationship with previous data on the postnatal expression of receptor protein and GIRK channel mRNA, our findings suggest that the maturation of GIRK current responses is determined predominantly by the different postnatal patterns of receptor expression.