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Regulation of the astrocyte resting membrane potential by cyclic AMP and protein kinase A
Author(s) -
Bolton Sally,
Greenwood Kirsty,
Hamilton Nicola,
Butt Arthur M.
Publication year - 2006
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20384
Subject(s) - hyperpolarization (physics) , forskolin , biology , intracellular , astrocyte , membrane potential , protein kinase a , endocrinology , resting potential , medicine , inward rectifier potassium ion channel , microbiology and biotechnology , biophysics , neuroscience , kinase , central nervous system , biochemistry , chemistry , receptor , stimulation , ion channel , organic chemistry , nuclear magnetic resonance spectroscopy
Abstract 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 μM 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 ∼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 μM 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. © 2006 Wiley‐Liss, Inc.