β-Adrenergic Modulation of Glial Inwardly Rectifying Potassium Channels
Version of Record online: 23 NOV 2002
Journal of Neurochemistry
Volume 64, Issue 4, pages 1576–1584, April 1995
How to Cite
Roy, M. L. and Sontheimer, H. (1995), β-Adrenergic Modulation of Glial Inwardly Rectifying Potassium Channels. Journal of Neurochemistry, 64: 1576–1584. doi: 10.1046/j.1471-4159.1995.64041576.x
- Issue online: 23 NOV 2002
- Version of Record online: 23 NOV 2002
- Resubmitted manuscript received June 20, 1994; revised manuscript received August 8, 1994; accepted September 9, 1994.
- K+ channel;
- Adenylate cyclase;
- Cyclic AMP
Abstract: Cultured spinal cord astrocytes (2–13 days in vitro) express several different potassium current types, including delayed rectifier, transient A-type, and inward rectifier (Kir) K+ currents. Of these, Kir is believed to be of critical importance in the modulation of extracellular [K+] in the CNS. Using the whole-cell patch-clamp technique, we analyzed modulation of Kir currents by β-adrenergic receptor activation. The selective β-adrenergic agonist isoproterenol (1–100 µM) and epinephrine (1–100 µM) each reduced peak Kir current amplitudes to 52.7 ± 12.5 and 63.6 ± 7.0%, respectively, at 100 µM. Forskolin (KD of ∼25 µM), an activator of adenylate cyclase (AC), and dibutyryl-cyclic AMP (1 mM), a membrane-permeable analogue of cyclic AMP (cAMP), were each used to increase [cAMP]i, the product of AC, and resulted in similar reductions of Kir currents. By contrast, 1,9-dideoxyforskolin (1–50 µM), a forskolin analogue that does not activate AC, did not affect Kir currents, indicating that AC activity is a required element for Kir modulation. Three inhibitors of PKA—Rp-adenosine 3′,5′-cyclic monophosphothioate, H-7, and adenosine 3′,5′-cyclic monophosphate-dependent protein kinase inhibitor—failed to inhibit Kir current reduction by β-adrenergic agonists. These results indicate that β-adrenergic receptor ligands can modulate Kir currents and suggest that this modulation involves activation of AC but not protein kinase A. Such modulation may provide a mechanism by which neurons can modulate glial Kir currents and thereby may affect glial K+“spatial buffering” in the CNS.