Metabotropic glutamate receptor activation enhances the activities of two types of Ca2+-activated k+ channels in rat hippocampal astrocytes. J Neurosci 2003 Mar 01;23(5):1678-87
Date
03/12/2003Pubmed ID
12629172Pubmed Central ID
PMC6741958DOI
10.1523/JNEUROSCI.23-05-01678.2003Scopus ID
2-s2.0-0037335453 (requires institutional sign-in at Scopus site) 76 CitationsAbstract
The influence of activation of glutamate receptor (GluR) on outward K(+) current in cultured neonate rat hippocampal astrocytes was investigated. Patch-clamp analysis of K(+) channel currents in cultured astrocytes identified the existence of 71 +/- 6 and 161 +/- 11 pS single-channel K(+) currents that were sensitive to changes in voltage and [Ca(2+)](i) and blocked by external TEA but not by charybdotoxin, iberiotoxin, apamin, or 4-aminopyridine. Reverse transcriptase (RT)-PCR and Northern blot analysis revealed transcripts of the Ca(2+)-activated K(+) channel (K(Ca)) beta(4)-subunit (beta4) (KCNMB4) in cultured astrocytes. Expression of the metabotropic glutamate receptor (mGluR) subtypes mGluR1 and mGluR5 and the ionotropic glutamate receptor (iGluR) subtypes iGluR1 and iGluR4 were detected by RT-PCR and immunofluorescence analysis in cultured astrocytes. The mGluR agonists L-glutamate and quisqualate increased the open state probability (NP(o)) of the 71 and 161 pS K(+) channel currents that were prevented by the mGluR receptor antagonists 1-aminoindan-1,5-dicarboxylic acid or L-(+)-2-amino-3-phosphonopropionic acid and not by the iGluR antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate or CNQX. Activation of the two types of K(+) channel currents by mGluR agonists was attenuated by pertussis toxin and by inhibition of phospholipase C (PLC) or cytochrome P450 arachidonate epoxygenase. These results indicate that brain astrocytes contain the KCNMB4 transcript and express two novel types of K(Ca) channels that are gated by activation of a G-protein coupled metabotropic glutamate receptor functionally linked to PLC and cytochrome P450 arachidonate epoxygenase activity.
Author List
Gebremedhin D, Yamaura K, Zhang C, Bylund J, Koehler RC, Harder DRMESH terms used to index this publication - Major topics in bold
AnimalsAstrocytes
Calcium
Cells, Cultured
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Enzyme Inhibitors
Excitatory Amino Acid Agonists
Excitatory Amino Acid Antagonists
Hippocampus
Large-Conductance Calcium-Activated Potassium Channel beta Subunits
Membrane Potentials
Nerve Tissue Proteins
Oxygenases
Patch-Clamp Techniques
Pertussis Toxin
Potassium
Potassium Channel Blockers
Potassium Channels
Potassium Channels, Calcium-Activated
Rats
Rats, Sprague-Dawley
Receptors, Metabotropic Glutamate
Type C Phospholipases
