Molecular mechanisms of microglial activation. B. Voltage- and purinoceptor-operated channels in microglia

Neurochem Int. 1996 Jul;29(1):13-24. doi: 10.1016/0197-0186(95)00133-6.

Abstract

Cultured, proliferating microglial cells can be further activated by lipopolysaccharide (LPS) and, thereby, turned into a non-proliferating state. While proliferating cells exhibit only inwardly rectifying potassium channels, non-proliferating cells express, in addition, outwardly rectifying potassium channels. The characteristics of the two channel populations are markedly different. Inward potassium currents inactivate and can be abolished by extracellular Cs+ and Ba2+. Outward potassium currents only slightly inactivate and can be abolished by 4-aminopyridine, quinine and charybdotoxin. An increase in the intracellular free Ca2+ concentration depresses the outward potassium current. ATP or its structural analogues stimulate two types of P2-purinoceptors on microglial cells, a ligand-activated cationic channel (P2x) which produces depolarization and a G protein coupled receptor (P2Y) which produces hyper-polarization via the opening of K+ channels. Both P2X- and P2Y-receptor stimulation may increase the intracellular Ca2+ concentration. In the former case, Ca2+ enters the cells via non-selective cationic channels. In the latter case, Ca2+ may be released from intracellular stores, owing to activation of the enzyme phospholipase C and subsequent generation of inositol 1,4,5-trisphosphate (IP3). It is assumed that neuronal damage leads to efflux of ATP into the extracellular space with subsequent activation of microglia. ATP-induced excessive depolarizations by P2X-purinoceptor stimulation may be counteracted by outwardly rectifying potassium channels and by hyperpolarizing P2Y-purinoceptors in non-proliferating microglia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Ion Channel Gating / physiology
  • Ion Channels / metabolism
  • Ion Channels / physiology*
  • Macrophage Activation / physiology*
  • Microglia / physiology*
  • Receptors, Purinergic / drug effects
  • Receptors, Purinergic / physiology

Substances

  • Ion Channels
  • Receptors, Purinergic