Second Messenger Modulation of Ion Channels
Schafer, Lisa L.
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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.