PT  - JOURNAL ARTICLE
AU  - De Koninck, P
AU  - Cooper, E
TI  - 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
AID  - 10.1523/JNEUROSCI.15-12-07966.1995
DP  - 1995 Dec 01
TA  - The Journal of Neuroscience
PG  - 7966--7978
VI  - 15
IP  - 12
4099  - http://www.jneurosci.org/content/15/12/7966.short
4100  - http://www.jneurosci.org/content/15/12/7966.full
SO  - J. Neurosci.1995 Dec 01; 15
AB  - 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 kinase A (PKA), protein kinase C (PKC), or tyrosine kinase do not affect nAChR transcript levels in these cultured neurons. The effect of membrane depolarization on alpha 7 expression is a result of Ca2+ influx through L-type Ca2+ channels, and we show that alpha 7 is upregulated through a Ca2+/calmodulin-dependent protein kinase (CaM kinase) pathway. The identification of CaM kinase as a link between activity and neurotransmitter receptor expression may indicate a novel mechanism that underlies some forms of synaptic plasticity.