PMID- 10485923
OWN - NLM
STAT- MEDLINE
DCOM- 19991014
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 19
DP  - 1999 Sep 14
TI  - Assignment of muscarinic receptor subtypes mediating G-protein modulation of
      Ca(2+) channels by using knockout mice.
PG  - 10899-904
AB  - There are five known subtypes of muscarinic receptors (M(1)-M(5)). We have used
      knockout mice lacking the M(1), M(2), or M(4) receptors to determine which
      subtypes mediate modulation of voltage-gated Ca(2+) channels in mouse sympathetic
      neurons. Muscarinic agonists modulate N- and L-type Ca(2+) channels in these
      neurons through two distinct G-protein-mediated mechanisms. One pathway is fast
      and membrane-delimited and inhibits N- and P/Q-type channels by shifting their
      activation to more depolarized potentials. The other is slow and
      voltage-independent and uses a diffusible cytoplasmic messenger to inhibit both
      Ca(2+) channel types. Using patch-clamp methods on acutely dissociated
      sympathetic neurons, we isolated each pathway by pharmacological and kinetic
      means and found that each one is nearly absent in a particular knockout mouse.
      The fast and voltage-dependent pathway is lacking in the M(2) receptor knockout
      mice; the slow and voltage-independent pathway is absent from the M(1) receptor
      knockout mice; and neither pathway is affected in the M(4) receptor knockout
      mice. The knockout effects are clean and are apparently not accompanied by
      compensatory changes in other muscarinic receptors.
FAU - Shapiro, M S
AU  - Shapiro MS
AD  - Department of Physiology and Biophysics, Box 357290, University of Washington
      School of Medicine, Seattle, WA 98195-7290, USA.
FAU - Loose, M D
AU  - Loose MD
FAU - Hamilton, S E
AU  - Hamilton SE
FAU - Nathanson, N M
AU  - Nathanson NM
FAU - Gomeza, J
AU  - Gomeza J
FAU - Wess, J
AU  - Wess J
FAU - Hille, B
AU  - Hille B
LA  - eng
GR  - R01 NS008174/NS/NINDS NIH HHS/United States
GR  - NS26920/NS/NINDS NIH HHS/United States
GR  - NS08174/NS/NINDS NIH HHS/United States
GR  - R37 NS008174/NS/NINDS NIH HHS/United States
GR  - R01 DA011322/DA/NIDA NIH HHS/United States
GR  - DA11322/DA/NIDA NIH HHS/United States
GR  - R01 NS026920/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
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 (Calcium Channels)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 5RY0UWH1JL (Oxotremorine)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - O3C74ACM9V (Ethylmaleimide)
SB  - IM
MH  - Animals
MH  - Calcium Channels/*metabolism
MH  - Ethylmaleimide/metabolism
MH  - GTP-Binding Proteins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Biological
MH  - Oxotremorine/metabolism
MH  - Patch-Clamp Techniques
MH  - Receptors, Muscarinic/*classification
MH  - Time Factors
MH  - Virulence Factors, Bordetella/metabolism
PMC - PMC17980
EDAT- 1999/09/15 00:00
MHDA- 1999/09/15 00:01
CRDT- 1999/09/15 00:00
PHST- 1999/09/15 00:00 [pubmed]
PHST- 1999/09/15 00:01 [medline]
PHST- 1999/09/15 00:00 [entrez]
AID - 10.1073/pnas.96.19.10899 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10899-904. doi:
      10.1073/pnas.96.19.10899.