Cyclic AMP-mediated regulation of the resting membrane potential in myelin-forming oligodendrocytes in the isolated intact rat optic nerve

Abstract

Myelin formation by oligodendrocytes has been shown to be regulated by cyclic AMP (cAMP) signaling pathways and to depend on the resting membrane potential (RMP). We therefore examined whether cAMP regulates the RMP of myelin-forming oligodendrocytes in isolated intact optic nerves of rats. Oligodendrocytes exhibited a significant developmental shift in the RMP from -37 mV at postnatal day (P)6-8 to -67 mV at P21-30. The regulation of RMP was examined further in myelin-forming oligodendrocytes in nerves aged P15-20. Raising intracellular cAMP with dbcAMP or forskolin induced a significant hyperpolarization in myelin-forming oligodendrocytes by 10-15 mV. Inhibition of cAMP-dependent protein kinase (PKA) with KT5720 depolarized the oligodendroglial RMP -30 mV, which was only partly reversed by dbcAMP. In contrast, inhibition of cAMP specific phosphodiesterase with rolipram had no significant effect on the oligodendroglial RMP or the cAMP-mediated hyperpolarization. Blockade of Kir with 100 microM BaCl(2) depolarized the oligodendrocyte RMP to -25 mV and inhibited the hyperpolarizing action of dbcAMP. The RMP was unaffected by agents that modulated ATP-sensitive potassium channels. The results provide evidence of a predominant role for Kir in setting the oligodendroglial RMP and show that cAMP regulates the oligodendroglial RMP, at least partly by a PKA-mediated pathway, possibly by modulating the activity of Kir.