title: Regulation of the astrocyte resting membrane potential by cyclic AMP and protein kinase A.
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 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.
authors.affiliation: School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom.
authors.forename: Sally
authors.initials: S
authors.lastname: Bolton
authors.forename: Kirsty
authors.initials: K
authors.lastname: Greenwood
authors.forename: Nicola
authors.initials: N
authors.lastname: Hamilton
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Butt
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000648:ultrastructure; D048430:Cell Shape / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004594:Electrophysiology; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D054086:KATP Channels; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D009900:Optic Nerve / Q000166:cytology / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000098854:Kcnj10 Channel
chemical_list: D005904:Glial Fibrillary Acidic Protein; D054086:KATP Channels; D000098854:Kcnj10 Channel; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011188:Potassium