XXXX and phorbol esters decrease the same K+ conductance in cultured oligodendrocytes.

@entity268 @entity2610 @entity859 @entity15227 @entity18650 @entity27625 @entity4515 @entity1359 @entity377 @entity972 @entity141 @entity1928
Cultured ovine oligodendrocytes (OLGs) express a number of voltage-dependent @entity972 currents after they attach to a substratum and as they begin to develop processes. At 24-48 hours following plating, an outward @entity972 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 @entity1928 and @entity1359 ( @entity4515 ) on OLG outward currents. These compounds are known to alter the myelinogenic metabolism of OLGs. @entity4515 , an activator of @entity27625 ( @entity27625 ), has been shown to enhance @entity2610 phosphorylation while @entity1928 acting on adenylate cyclase, and thereby increasing @entity268 , inhibits it. Both @entity1928 and @entity4515 increase the phosphorylation of 2'3'-cyclic @entity377 phosphodiesterase, an OLG/myelin protein. We found that @entity1928 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 @entity1928 was attenuated when the adenylate cyclase inhibitor @entity859 (2 mM) was present in the intracellular/pipette filling solution. The results of @entity4515 experiments were similar to those obtained with @entity1928 . Whereas the amplitude of the currents in the presence of @entity4515 was reduced by 28% at 1.5 nM and 60% and 600 nM, the decay phase of the peak currents was less affected. The @entity4515 effect could still be seen when the intracellular @entity141 was reduced to less than or equal to 10 nM with 5 mM @entity18650 , but was inhibited when the cells were pre-exposed to 50 microM @entity15227 , a @entity27625 inhibitor. It is postulated that the @entity972 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.
