Baines, Richard A.. (2003) Postsynaptic protein kinase a reduces neuronal excitability in response to increased synaptic excitation in the Drosophila CNS. Journal of Neuroscience, Vol.23 (No.25). pp. 8664-8672. ISSN 0270-6474

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Abstract

Previous work has identified a role for synaptic activity in the development of excitable properties of motoneurons in the Drosophila embryo. In this study the underlying mechanism that enables two such neurons, termed aCC and RP2, to respond to increased exposure to synaptic excitation is characterized. Synaptic excitation is increased in genetic backgrounds that lack either a cAMP-specific phosphodiesterase (EC:3.1.4, dunce) or acetylcholinesterase (EC:3.1.1.7, ace), the enzyme that terminates the endogenous cholinergic excitation of these motoneurons. Analysis of membrane excitability in aCC/RP2, in either background, shows that these neurons have a significantly reduced capability to fire action potentials (APs) in response to injection of depolarizing current. Analysis of underlying voltage-gated currents show that this effect is associated with a marked reduction in magnitude of the voltage-dependent inward Na+ current (INa). Partially blocking INa in these motoneurons, using low concentrations of TTX, demonstrates that a reduction of INa is, by itself, sufficient to reduce membrane excitability. An analysis of firing implicates an increased AP threshold to underlie the reduction in membrane excitability observed because of heightened exposure to synaptic excitation. Genetic or pharmacological manipulations that either elevate cAMP or increase protein kinase A (PKA) activity in wild-type aCC/RP2 mimic both the reductions in membrane excitability and INa. In comparison, increasing cAMP catabolism or inhibition of PKA activity is sufficient to block the induction of these activity-dependent changes. The induced changes in excitability can be rapid, occurring within 5 min of exposure to a membrane-permeable cAMP analog, indicative that threshold can be regulated in these neurons by a post-translational mechanism that is dependent on phosphorylation.

Item Type:	Journal Article
Alternative Title:	Postsynaptic protein kinase a reduces neuronal excitability in response to increased synaptic excitation in the Drosophila central nervous system
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Q Science > QL Zoology
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Central nervous system stimulants, Neural transmission -- Regulation, Excitation (Physiology), Homeostasis, Drosophila -- Physiology
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Date:	24 September 2003
Volume:	Vol.23
Number:	No.25
Page Range:	pp. 8664-8672
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	Royal Society (Great Britain), Wellcome Trust (London, England)
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URI:	http://wrap.warwick.ac.uk/id/eprint/2560

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