Different localizations and functions of L-type and N-type calcium channels during development of hippocampal neurons

Using immunocytochemical assays and patch-clamp and calcium-imaging recordi ngs, we demonstrate that L-type and N-type calcium channels have distinct p atterns of expression and distribution and play different functional roles during hippocampal neuron differentiation. L-type channels, which support t he depolarization-induced calcium influx in neurons from the very early dev elopmental stages, are functionally restricted to the somatodendritic compa rtment throughout neuronal development and play a crucial role in supportin g neurite outgrowth at early developmental stages. N-type channels, which s tart contributing at later neuronal differentiation stages (3-4 DIV), are a lso functionally expressed in the axons of immature neurons. At this develo pmental stage preceding synaptogenesis, N-type (but not L-type) channels ar e involved in controlling synaptic vesicle recycling. Pt is only at later d evelopmental stages (10-12 DIV), when the neurons have established a clear axodendritic polarity and form synaptic contacts, that N-type channels are progressively excluded from the axon. Electrophysiological recordings of si ngle neurons growing in microislands revealed that synaptic maturation coin cides with a progressive increase in N-type channels in the somatodendritic region and a progressive decrease in the N-type channels supporting glutam ate release from the presynaptic terminal. These results indicate that L-ty pe and N-type calcium channels undergo dynamic, developmentally regulated r earrangements in regional distribution and function and also suggest that d ifferent mechanisms may be involved in the sorting and/or stabilization of these two types of channels in different plasma membrane domains during neu ronal differentiation. (C) 2000 Academic Press.