Emergence of a functional coupling between inositol-1,4,5-trisphosphate receptors and calcium channels in developing neocortical neurons

Cortical pyramidal neurons are considered to be less excitable in the immature cortex than in adults. Our previous report revealed that a negative feedback regulation of membrane excitability is highly correlated with a novel form of calcium release from inositol-1,4,5-trisphosphate (IP3)-sensitive calcium stores (IP3-assisted calcium-induced calcium release) in neocortical pyramidal neurons under muscarinic cholinergic activation. As a step to understand the ground for the low membrane excitability in immature tissue, we examined development Of IP3-assisted calcium-induced calcium release. In visual cortex neurons from 'juvenile' rats (2-3 weeks of age), an enhancement of spike-frequency adaptation occurred at high spike-frequencies (16 22 Hz), whereas the reduction was observed at low frequencies (6-10 Hz). IP3-assisted calcium-induced calcium release occurred at the higher frequencies only. In 'early' postnatal tissue (1 week of age), by contrast, at neither high nor low frequencies did this form of calcium release occur, and muscarinic cholinergic activation always induced a reduction of spike-frequency adaptation at any spike-frequencies. The mechanism for the failure of induction of IP3-assisted calcium-induced calcium release in 'early' postnatal tissue was investigated. Both an ample supply of calcium influx, elicited by higher frequency spike trains, and a supplementary injection Of IP3 through whole-cell pipets, combined together or applied alone, failed to enable IP3-assisted calcium-induced calcium release in 'early' postnatal tissue. Muscarinic cholinergic activation alone induced a conventional IP3-induced calcium release similar to that observed in neurons from 'juvenile' tissue. Together, it is most likely that functional IP(3)Rs and calcium channels are already present and functional, but are not yet adequately assembled to allow IP3-assisted calcium-induced calcium release in cortical pyramidal neurons from rats of 1 week old. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.