Research article summary (published 30 Aug 2009):

Ca2+- and thromboxane-dependent distribution of MaxiK channels in cultured astrocytes: from microtubules to the plasma membrane.

Full Abstract

Large-conductance, voltage- and Ca2+-activated K+ channels (MaxiK) are broadly expressed ion channels minimally assembled by four pore-forming alpha-subunits (MaxiKalpha) and typically observed as plasma membrane proteins in various cell types. In murine astrocyte primary cultures, we show that MaxiKalpha is predominantly confined to the microtubule network. Distinct microtubule distribution of MaxiKalpha was visualized by three independent labeling approaches: (1) MaxiKalpha-specific antibodies, (2) expressed EGFP-labeled MaxiKalpha, and (3) fluorophore-conjugated iberiotoxin, a specific MaxiK pore-blocker. This MaxiKalpha association with microtubules was further confirmed by in vitro His-tag pulldown, co-immunoprecipitation from brain lysates, and microtubule depolymerization experiments. Changes in intracellular Ca2+ elicited by general pharmacological agents, caffeine or thapsigargin, resulted in increased MaxiKalpha labeling at the plasma membrane. More notably, U46619, an analog of thromboxane A2 (TXA2), which triggers Ca2+-release pathways and whose levels increase during cerebral hemorrhage/trauma, also elicits a similar increase in MaxiKalpha surface labeling. Whole-cell patch clamp recordings of U46619-stimulated cells develop a approximately 3-fold increase in current amplitude indicating that TXA2 stimulation results in the recruitment of additional, functional MaxiK channels to the surface membrane. While microtubules are largely absent in mature astrocytes, immunohistochemistry results in brain slices show that cortical astrocytes in the newborn mouse (P1) exhibit a robust expression of microtubules that significantly colocalize with MaxiK. The results of this study provide the novel insight that suggests that Ca2+ released from intracellular stores may play a key role in regulating the traffic of intracellular, microtubule-associated MaxiK stores to the plasma membrane of developing murine astrocytes.

Author information

Author/s: Ou, J W (JW); Kumar, Y (Y); Alioua, A (A); Sailer, C (C); Stefani, E (E); Toro, L (L);

Affiliation: Department of Molecular and Medical Pharmacology, University of California at Los Angeles, Los Angeles, California, USA.

Grants: HL088640 (Agency:NHLBI NIH HHS) ; HL54970 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Glia (Glia), published in United States. (Language: eng)

Reference: 2009-Sep; vol 57 (issue 12) : pp 1280-95

Dates: Created 2009/07/20; Completed 2009/11/02;

PMID: 19170178, status: MEDLINE (last retrieval date: 11/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology Animals Animals, Newborn Astrocytes - drug effects; metabolism Brain - drug effects; metabolism Caffeine - pharmacology Calcium - metabolism Cell Membrane - drug effects; physiology Cells, Cultured Central Nervous System Agents - pharmacology

Chelating Agents - pharmacology Egtazic Acid - analogs & derivatives; pharmacology Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - antagonists & inhibitors; metabolism Membrane Potentials - drug effects; physiology Mice Mice, Inbred C57BL Microtubules - metabolism Thapsigargin - pharmacology Thromboxane A2 - analogs & derivatives Tubulin - metabolism

Associated Chemicals: Central Nervous System Agents (0) ; Chelating Agents (0) ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits (0) ; Tubulin (0) ; 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester (139890-68-9) ; Thromboxane A2 (57576-52-0) ; Caffeine (58-08-2) ; Egtazic Acid (67-42-5) ; Thapsigargin (67526-95-8) ; Calcium (7440-70-2) ; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid (76898-47-0)

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