Biomedical subjects

Sally Bolton

Publications and source records attributed to Sally Bolton.

3 recordsLinked to original sources

PubMed2006

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

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.

Age Factors↗

PubMed2006

Regulation of the astrocyte resting membrane potential by cyclic AMP and protein kinase A.

The factors regulating astroglial resting membrane potential (RMP) are unresolved. Here, we have examined developmental, morphological, and intracellular factors that may regulate the RMP in astrocytes of isolated intact optic nerves of rats and mice aged postnatal day (P3) to adult. The astroglial RMP ranged from -25 to -85 mV, independent of age and morphological phenotype. There was a developmental negative shift in the astroglial RMP from a non-Gaussian distribution in perinatal nerves, to a bimodal distribution of RMPs after P15, with peaks at -52 and -74 mV in adults. Blockade of Kir with 100 microM BaCl(2) significantly depolarized the RMP to -30 mV; the RMP was unaffected by TEA or agents that modulated ATP-sensitive potassium channels. Raising intracellular cyclic AMP (cAMP) with dbcAMP or forskolin induced a significant hyperpolarization by approximately 15 mV, whereas inhibition of cAMP-dependent protein kinase (PKA) depolarized the astroglial RMP to -40 mV. The hyperpolarizing action of dbcAMP was blocked by 100 microM BaCl(2). The effects of BaCl(2) indicate that the developmental negative shift in the RMP and the cAMP-mediated hyperpolarization were dependent on Kir. This study provides evidence that the heterogeneous RMP of mature astrocytes is regulated by cAMP and PKA signaling.

Animals↗

PubMedDate not supplied

The optic nerve: a model for axon-glial interactions.

The rodent optic nerve is a model tissue for the physiological investigation of axonal-glial interactions in a typical CNS white matter tract. There is strong evidence that nerve transmission is maintained by a considerable degree of dynamic signalling between axons and glia through a variety of mechanisms, such as regulation of the ionic environment, energy metabolism and calcium signalling. This review focuses on the methods used to examine axonal and glial functions and interactions, primarily in the rodent optic nerve. Techniques encompass intracellular microelectrodes, sucrose- and grease-gap recordings of membrane potentials, suction electrode to measure compound action potentials, the use of ion-sensitive electrodes, patch clamping and imaging. An overview of the advantages and drawbacks of each technique is given and the application of each to the understanding glial and axonal physiology is briefly discussed.

Animals↗