Document Detail

Forskolin and phorbol esters decrease the same K+ conductance in cultured oligodendrocytes.
MedLine Citation:
PMID:  3216367     Owner:  NLM     Status:  MEDLINE    
Cultured ovine oligodendrocytes (OLGs) express a number of voltage-dependent potassium currents after they attach to a substratum and as they begin to develop processes. At 24-48 hours following plating, an outward potassium current can be identified that represents a composite response of a rapidly inactivating component and a steady-state or noninactivating component. After 4-7 days in culture, OLGs also develop an inward rectifier current. We studied the effects of forskolin and phorbol 12-myristate 13-acetate (PMA) on OLG outward currents. These compounds are known to alter the myelinogenic metabolism of OLGs. PMA, an activator of protein kinase C (PK-C), has been shown to enhance myelin basic protein phosphorylation while forskolin acting on adenylate cyclase, and thereby increasing cAMP, inhibits it. Both forskolin and PMA increase the phosphorylation of 2'3'-cyclic nucleotide phosphodiesterase, an OLG/myelin protein. We found that forskolin decreased the steady-state outward current at 120 mV by 10% at 100 nM, and by 72% at 25 microM from a holding potential of -80 mV. The time course of inactivation of the peak currents was decreased, affecting both the fast and slow time constants. There was no significant change in the steady-state parameters of current activation and inactivation. The effect of forskolin was attenuated when the adenylate cyclase inhibitor adenosine (2 mM) was present in the intracellular/pipette filling solution. The results of PMA experiments were similar to those obtained with forskolin. Whereas the amplitude of the currents in the presence of PMA was reduced by 28% at 1.5 nM and 60% and 600 nM, the decay phase of the peak currents was less affected. The PMA effect could still be seen when the intracellular Ca2+ was reduced to less than or equal to 10 nM with 5 mM BAPTA, but was inhibited when the cells were pre-exposed to 50 microM psychosine, a PK-C inhibitor. It is postulated that the potassium currents in OLG can be physiologically modulated by two distinct second-messenger systems, perhaps converging at the level of a common phosphorylated enzyme or regulatory protein.
B Soliven; S Szuchet; B G Arnason; D J Nelson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of membrane biology     Volume:  105     ISSN:  0022-2631     ISO Abbreviation:  J. Membr. Biol.     Publication Date:  1988 Oct 
Date Detail:
Created Date:  1989-03-09     Completed Date:  1989-03-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0211301     Medline TA:  J Membr Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  177-86     Citation Subset:  IM    
Department of Neurology, University of Chicago, Illinois 60637.
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MeSH Terms
Cells, Cultured
Electric Conductivity
Forskolin / pharmacology*
Membrane Potentials / drug effects
Neuroglia / drug effects*
Oligodendroglia / cytology,  drug effects*,  physiology
Phorbol Esters / pharmacology*
Potassium / physiology*
Second Messenger Systems
Tetradecanoylphorbol Acetate / pharmacology
Grant Support
Reg. No./Substance:
0/Phorbol Esters; 16561-29-8/Tetradecanoylphorbol Acetate; 66428-89-5/Forskolin; 7440-09-7/Potassium

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