Activation of endothelin receptors by sarafotoxin regulates Ca2+ homeostasis in cerebellar astrocytes

James A. Holzwarth, Steven R. Glaum, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

We carried out experiments designed to investigate the effects of sarafotoxin‐6B (SFTx) on [Ca2+]i in cerebellar astrocytes using the Ca2+ indicator fura‐2. Both endothelin‐1 and sarafotoxin‐6B increased [Ca2+]i in individual cerebellar astrocytes in cell culture. The shape of the response was variable but usually consisted of an initial peak of [Ca2+]i followed by an extended plateau increase in [Ca2+]i. In Ca2+‐free medium only the initial peak was observed. If Ca2+ was subsequently readmitted to the external medium a plateau was now formed. When external Ca2+ was removed during a plateau, [Ca2+]i rapidly declined; replacing the external Ca2+ reversed this decline. The plateau was also reversibly reduced by addition of Ni2+ (5 mM) to the external medium. Addition of 50 mM K+ produced a small increase in [Ca2+]i in most cells. This response was blocked by nimodipine. However, nimodipine only slightly blocked the plateau increase in [Ca2+]i that was formed following activation of endothelin receptors. Furthermore, perfusion of cells with 50 mM K+ during the plateau portion of a response to SFTx reduced [Ca2+]i. In some cells addition of a phorbol ester produced a sustained increase in [Ca2+]i that was blocked by nimodipine. In conclusion, activation of endothelin receptors by SFTx in cerebellar astrocytes produces both Ca2+ mobilization and Ca2+ influx. The pathway for Ca2+ influx is predominantly a non‐voltage‐dependent one, although some entry through a dihydropyridine‐sensitive pathway also appears to occur. Furthermore, activation of protein kinase C in cerebellar astrocytes activates voltage‐sensitive Ca2+ channels. © 1992 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)239-250
Number of pages12
JournalGLIA
Volume5
Issue number4
DOIs
StatePublished - Jan 1 1992

Keywords

  • Calcium mobilization
  • Dihydropyridines
  • Fura‐2
  • Phorbol esters

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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