PMID: 8613734Dec 1, 1995Paper

Differential regulation of neuronal nicotinic ACh receptor subunit genes in cultured neonatal rat sympathetic neurons: specific induction of alpha 7 by membrane depolarization through a Ca2+/calmodulin-dependent kinase pathway

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
P De Koninck, E Cooper

Abstract

We have examined the regulation of neuronal nicotinic ACh receptor (nAChR) genes and ACh-evoked currents by neonatal rat sympathetic neurons developing in culture. These neurons contain 5 nAChR transcripts: alpha 3, alpha 5, alpha 7, beta 2, and beta 4. When developing in culture, the neurons express 4 of these transcripts, alpha 3, alpha 5, beta 2, and beta 4, at levels similar to those in neurons developing in vivo: alpha 3 mRNA levels increase two- to threefold over the first week, whereas the levels for alpha 5, beta 2, and beta 4 remain essentially constant. In contrast, alpha 7 mRNA levels drop by 60-75% within the first 48 hr and remain low. We show that during the first week, the ACh-evoked current densities on these cultured neurons increase twofold and correlate well with the increase in alpha 3 mRNA levels. Depolarizing the neurons with 40 mM KCl for 1-2 d upregulates the alpha 7 gene; this specific change in alpha 7 mRNA level correlates with an increase in alpha-bungarotoxin (alpha-BTX) binding on the surface of the neurons. Depolarization has little effect on the expression of the other four transcripts, or on the magnitude or kinetics of the ACh-evoked currents. Furthermore, activators or inhibitors of protein ki...Continue Reading

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