Journal article
Distinct Roles of CaMKII and PKA in Regulation of Firing Patterns and K+ Currents in Drosophila Neurons
Journal of neurophysiology, Vol.85(4), pp.1384-1394
04/01/2001
DOI: 10.1152/jn.2001.85.4.1384
PMID: 11287463
Abstract
The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the cAMP-dependent protein kinase A (PKA) cascades have been implicated in neural mechanisms underlying learning and memory as supported by mutational analyses of the two enzymes in Drosophila. While there is mounting evidence for their roles in synaptic plasticity, less attention has been directed toward their regulation of neuronal membrane excitability and spike information coding. Here we report genetic and pharmacological analyses of the roles of PKA and CaMKII in the firing patterns and underlying K+ currents in cultured Drosophilacentral neurons. Genetic perturbation of the catalytic subunit of PKA ( DC0) did not alter the action potential duration but disrupted the frequency coding of spike-train responses to constant current injection in a subpopulation of neurons. In contrast, selective inhibition of CaMKII by the expression of an inhibitory peptide in ala transformants prolonged the spike duration but did not affect the spike frequency coding. Enhanced membrane excitability, indicated by spontaneous bursts of spikes, was observed in CaMKII-inhibited but not in PKA-diminished neurons. In wild-type neurons, the spike train firing patterns were highly reproducible under consistent stimulus conditions. However, disruption of either of these kinase pathways led to variable firing patterns in response to identical current stimuli delivered at a low frequency. Such variability in spike duration and frequency coding may impose problems for precision in signal processing in these protein kinase learning mutants. Pharmacological analyses of mutations that affect specific K+ channel subunits demonstrated distinct effects of PKA and CaMKII in modulation of the kinetics and amplitude of different K+ currents. The results suggest that PKA modulates Shaker A-type currents, whereas CaMKII modulates Shal-A type currents plus delayed rectifier Shab currents. Thus differential regulation of K+ channels may influence the signal handling capability of neurons. This study provides support for the notion that, in addition to synaptic mechanisms, modulations in spike activity patterns may represent an important mechanism for learning and memory that should be explored more fully.
Details
- Title: Subtitle
- Distinct Roles of CaMKII and PKA in Regulation of Firing Patterns and K+ Currents in Drosophila Neurons
- Creators
- Wei-Dong Yao - Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242Chun-Fang Wu - Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Journal of neurophysiology, Vol.85(4), pp.1384-1394
- DOI
- 10.1152/jn.2001.85.4.1384
- PMID
- 11287463
- ISSN
- 0022-3077
- eISSN
- 1522-1598
- Language
- English
- Date published
- 04/01/2001
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984070720202771
Metrics
33 Record Views