CONTACT-DEPENDENT REGULATION OF N-TYPE CALCIUM-CHANNEL SUBUNITS DURING SYNAPTOGENESIS

The developmental regulation of the N-type calcium channel during syna ptogenesis mas studied using cultured rat hippocampal neurons to eluci date the roles of extrinsic versus intrinsic cues in the expression an d distribution of this channel Prior to synapse formation, alpha(1B) a nd beta(3) subunits of the N-type calcium channel were distributed dif fusely throughout neurites, growth cones, and somata, As synaptogenesi s proceeded, the subunit distributions became punctate and colocalized with the synaptic vesicle protein synaptotagmin, Isolated neurons wer e also examined to test for the requirement of extrinsic cues that con trol N-type calcium channel expression and distribution, These neurons expressed N-type calcium channel subunits, but their distributions re mained diffuse. Functional omega-conotoxin GVIA-sensitive channels wer e expressed in isolated neurons, although the distribution of alpha(1B ) subunits was diffuse. The distribution of the alpha(1B) subunit and synaptotagmin only became punctate when neuron-neuron contact was allo wed. Thus, the expression of functional N-type calcium channels is the result of an intrinsic program while extrinsic regulatory sues mediat ed by neuron-neuron contact are required to central their distribution during synaptogenesis. (C) 1998 John Wiley & Sons. Inc.