PMID- 9844003
OWN - NLM
STAT- MEDLINE
DCOM- 19990114
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 95
IP  - 25
DP  - 1998 Dec 8
TI  - Human gamma-aminobutyric acid type B receptors are differentially expressed and 
      regulate inwardly rectifying K+ channels.
PG  - 14991-6
AB  - gamma-Aminobutyric acid type B receptors (GABABRs) are involved in the fine 
      tuning of inhibitory synaptic transmission. Presynaptic GABABRs inhibit 
      neurotransmitter release by down-regulating high-voltage activated Ca2+ channels, 
      whereas postsynaptic GABABRs decrease neuronal excitability by activating a 
      prominent inwardly rectifying K+ (Kir) conductance that underlies the late 
      inhibitory postsynaptic potentials. Here we report the cloning and functional 
      characterization of two human GABABRs, hGABABR1a (hR1a) and hGABABR1b (hR1b). 
      These receptors closely match the pharmacological properties and molecular 
      weights of the most abundant native GABABRs. We show that in transfected 
      mammalian cells hR1a and hR1b can modulate heteromeric Kir3.1/3.2 and Kir3.1/3.4 
      channels. Heterologous expression therefore supports the notion that Kir3 
      channels are the postsynaptic effectors of GABABRs. Our data further demonstrate 
      that in principle either of the cloned receptors could mediate inhibitory 
      postsynaptic potentials. We find that in the cerebellum hR1a and hR1b transcripts 
      are largely confined to granule and Purkinje cells, respectively. This finding 
      supports a selective association of hR1b, and not hR1a, with postsynaptic Kir3 
      channels. The mapping of the GABABR1 gene to human chromosome 6p21.3, in the 
      vicinity of a susceptibility locus (EJM1) for idiopathic generalized epilepsies, 
      identifies a candidate gene for inherited forms of epilepsy.
FAU - Kaupmann, K
AU  - Kaupmann K
AD  - Novartis Pharma AG, TA Nervous System, CH-4002 Basel, Switzerland.
FAU - Schuler, V
AU  - Schuler V
FAU - Mosbacher, J
AU  - Mosbacher J
FAU - Bischoff, S
AU  - Bischoff S
FAU - Bittiger, H
AU  - Bittiger H
FAU - Heid, J
AU  - Heid J
FAU - Froestl, W
AU  - Froestl W
FAU - Leonhard, S
AU  - Leonhard S
FAU - Pfaff, T
AU  - Pfaff T
FAU - Karschin, A
AU  - Karschin A
FAU - Bettler, B
AU  - Bettler B
LA  - eng
SI  - GENBANK/AJ225028
SI  - GENBANK/AJ225029
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Potassium Channels)
RN  - 0 (Receptors, GABA-B)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - COS Cells
MH  - Cricetinae
MH  - Electrophysiology
MH  - Humans
MH  - Ion Channel Gating
MH  - Molecular Sequence Data
MH  - Potassium Channels/*physiology
MH  - Receptors, GABA-B/*physiology
MH  - Transfection
PMC - PMC24563
EDAT- 1998/12/09 00:00
MHDA- 1998/12/09 00:01
PMCR- 1999/06/08
CRDT- 1998/12/09 00:00
PHST- 1998/12/09 00:00 [pubmed]
PHST- 1998/12/09 00:01 [medline]
PHST- 1998/12/09 00:00 [entrez]
PHST- 1999/06/08 00:00 [pmc-release]
AID - 3835 [pii]
AID - 10.1073/pnas.95.25.14991 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14991-6. doi: 
      10.1073/pnas.95.25.14991.