The Journal of Neuroscience, March 1, 2003, 23(5):1678
Metabotropic Glutamate Receptor Activation Enhances the
Activities of Two Types of Ca2+-Activated K+
Channels in Rat Hippocampal Astrocytes
Debebe
Gebremedhin1, 2,
Ken
Yamaura1, 2,
Chenyang
Zhang1, 2,
Johan
Bylund1, 2,
Raymond C.
Koehler4, and
David R.
Harder1, 2, 3
1 Department of Physiology and
2 Cardiovascular Research Center, Medical College of
Wisconsin and 3 Clement Zablocki Veterans Affairs
Medical Center, Milwaukee, Wisconsin 53226, and
4 Departments of Anesthesiology and Critical Care Medicine,
Johns Hopkins University School of Medicine, Baltimore, Maryland 21287
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 [Ca2+]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 Ca2+-activated
K+ channel (KCa)
4-subunit (4) (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 (NPo) 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 KCa channels that are gated by
activation of a G-protein coupled metabotropic glutamate receptor
functionally linked to PLC and cytochrome P450 arachidonate epoxygenase activity.
Key words:
neonate rat hippocampus; cultured astrocytes; excitatory amino acids; glutamate receptors; patch-clamp recording; Ca2+-activated K+ channels; KCNMB4; neuronal activity
Copyright © 2003 Society for Neuroscience 0270-6474/03/2351678-10$05.00/0
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