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The Journal of Neuroscience, June 1, 1998, 18(11):4001-4007
Pore Mutation in a G-Protein-Gated Inwardly Rectifying
K+ Channel Subunit Causes Loss of K+-Dependent
Inhibition in weaver Hippocampus
Wolfgang
Jarolimek1,
Jörg
Bäurle2, and
Ulrich
Misgeld1
1 I.Physiologisches Institut, Universität
Heidelberg, D-69120 Heidelberg, Germany, and 2 Freie
Universität Berlin, Fachbereich Humanmedizin,
Universitätsklinikum Benjamin Franklin, Physiologisches Institut,
D-14195 Berlin, Germany
Weaver (wv) mice carry a point
mutation in the pore region of a G-protein-gated inwardly rectifying
K+ channel subunit (Kir3.2). wvKir3.2
conducts inward currents that may cause the loss of neurons in the
cerebellum and substantia nigra. Although Kir3.2 is widely expressed in
the CNS, significant morphological or physiological changes have not
been reported for other brain areas. We studied the role of
wvKir3.2 in hippocampal slices of young [postnatal day
(P) 4-18] and adult wv/wv ( P24) mice, because
protein levels of Kir 3.1 and Kir3.2 appear to be normal in the first 3 postnatal weeks and only decrease thereafter. In disinhibited slices,
the GABAB receptor agonist R-baclofen reduced burst activity in wv/wv mice but was much more
potent in wild-type mice. Mean resting membrane potential, slope input resistance, and membrane time constant of CA3 neurons of adult wv/wv and wild-type mice were indistinguishable.
However, R-baclofen or chloroadenosine did not induce
K+ currents or any other conductance change in
wv/wv mice. Moreover, electrical or chemical stimulation
of inhibitory neurons did not evoke slow IPSPs in adult
wv/wv mice. Only in a few cells of young wv/wv mice did GABAB receptor activation by
R-baclofen or presynaptic stimulation induce small
inward currents, which were likely caused by a Na+
ion influx through wvKir3.2 channels. The data show that
the pore mutation in wvKir3.2 channels results in a
hippocampal phenotype resembling Kir3.2-deficient mutants, although it
is not associated with the occurrence of seizures.
Key words:
weaver; hippocampus; R-baclofen; slow IPSPs; Kir3.2; GIRK2; G-protein-activated potassium currents; adenosine; serotonin; GABAB receptors
Copyright © 1998 Society for Neuroscience 0270-6474/98/18114001-07$05.00/0
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