PubMed Journals: J Biol Chem
Source: PMID: 11713246
⇦ ⇨ J Biol Chem. 2002 Jan 18;277(3):1974-80.
⇩ Epub 2001 Nov 16.
Transforming growth factor-beta 1 regulates
Kir2.3 inward rectifier K+ channels via
phospholipase C and protein kinase C-delta
in reactive astrocytes from adult rat brain.
Perillan PR(1), Chen M, Potts EA, Simard
(1) Department of Neurosurgery,
University of Maryland School of Medicine,
Baltimore, Maryland 21201, USA.
The multifunctional cytokine, transforming
growth factor beta(1) (TGF-beta(1)), exerts
complex effects on astrocytes with early
signaling events being less well characterized
than transcriptional mechanisms. We examined
the effect of TGF-beta(1) on the 14-pS Kir2.3
inward rectifier K(+) channel in rat primary
cultured reactive astrocytes. Immunofluorescence
study showed that cells co-expressed TGF-beta(1)
receptors 1 and 2, Kir2.3, and
glial fibrillary acidic protein (GFAP).
Patch clamp study showed that TGF-beta(1)
(0.1-100 ng/ml) caused a rapid (<5 min)
depolarization because of dose-dependent
down-regulation of Kir2.3 channels, which
was mimicked by the protein kinase C (PKC)
activator phorbol 12-myristate 13-acetate
(10-500 nm) and which was inhibited by the
PKC inhibitor calphostin C (100 nm), by
PKC desensitization produced by 3 h of exposure
to phorbol 12-myristate 13-acetate (100
nm), and by the PKC-delta isoform-specific
inhibitor rottlerin (50 microm). Immunoblot
analysis and confocal imaging showed that
TGF-beta(1) caused PKC-delta translocation
to membrane, and co-immunoprecipitation
experiments showed that TGF-beta(1) enhanced
association between Kir2.3 and PKC-delta.
Additional electrophysiological experiments showed that
Kir2.3 channel down-regulation was blocked
by the phospholipase C inhibitors, neomycin
(100 microm) and D609 (200 microm). Given
the commonality of signaling involving
PLC-PKC-delta, we speculate that TGF-beta(1)-evoked
depolarization may be an early signaling
event related to gene transcription in astrocytes.
DOI: 10.1074/jbc.M107984200 PMID: 11713246
[Indexed for MEDLINE]