Second Messenger Modulation of Ion Channels
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Authors
Schafer, Lisa L.
Issue Date
1991
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
The N1E-115 cell line of murine neuroblastoma cells can be induced
to differentiate by the removal of serum from the culture medium to study
the process of neuronal differentiation. Morphological (the extension of
neurites) and electrophysiological (the ability to generate sodium-dependent
action potentials) differentiation do not occur simultaneously
(Cosgrove and Cobbett, 1991). However, it has been shown that sodium
channels are present in the membrane from the onset of morphological
differentiation and then become functional (capable of conducting sodium
ions) during physiological differentiation (DeConinck and Cobbett, 1991). To
increase our understanding of neuronal development, the modulation of
sodium channels was studied by investigating mechanisms that control
morphological and electrophysiological differentiation. Effects of forskolin
(which raises cAMP levels and/or increases the activity of protein kinase A)
and 1,9-dideoxyforskolin (which is a homolog of forskolin that does not raise
cAMP levels) on undifferentiated and differentiated cells were examined.
Forskolin and 1,9-dideoxyforskolin had similar effects on undifferentiated
cells, causing a reduction of the potassium current with no change in the
sodium current. Differentiated cells are incapable of generating an action
potential in the presence of forskolin but can still generate an action
potential in the presence of 1,9-dideoxyforskolin. Since forskolin is believed
to activate the adenyl ate cyclase pathway (Seamon and Daly, 1986) while 1,9-
dideoxyforskolin does not, phosphorylation of sodium channels in intact
NIE-115 differentiated cells could be an important mechanism in
regulating the electrical excitability of the nerve cell.
Description
iii, 35 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.