PMID- 16567411
OWN - NLM
STAT- MEDLINE
DCOM- 20071025
LR  - 20151119
IS  - 0021-924X (Print)
IS  - 0021-924X (Linking)
VI  - 139
IP  - 3
DP  - 2006 Mar
TI  - Muscarinic acetylcholine receptors activate TRPC6 channels in PC12D cells via 
      Ca2+ store-independent mechanisms.
PG  - 459-70
AB  - In this paper we report that stimulation of mAChRs in PC12D cells activates Ca2+ 
      channels that are regulated independently of intracellular Ca2+ stores. In 
      nominally Ca2+-free medium, exposure of PC12D cells to carbachol stimulates a 
      robust influx of Ba2+, a Ca2+ substitute. This influx is blocked by atropine, but 
      not by inhibitors of the nicotinic acetylcholine receptor or L-, N-, or T-type 
      voltage-regulated Ca2+ channels. By contrast, depletion of intracellular Ca2+ 
      stores with thapsigargin only weakly stimulates Ba2+ influx. Unlike 
      store-operated Ca2+ channels (SOCCs), which close only after intracellular Ca2+ 
      stores refill, channels mediating carbachol-stimulated Ba2+ influx rapidly close 
      following the inactivation of mAChRs with atropine. Ba2+ influx is inhibited by 
      extracellular Ca2+, by the Ca2+ channel blocker SKF-96365, and by activation of 
      protein kinase C (PKC). Exogenous expression of antisense RNA encoding the rat 
      canonical-transient receptor potential Ca2+ channel subtype 6 (TRPC6) or the 
      N-terminal domain of TRPC6 blocks carbachol-stimulated Ba2+ influx in PC12D 
      cells. Expression of TRPC6 antisense RNA or the TRPC6 N-terminal domain also 
      blocks Ba2+ influx stimulated by 1-oleoyl-2-acetyl-sn-glycerol (OAG), a 
      diacylglycerol analog previously shown to activate exogenously expressed TRPC6 
      channels. These data show that mAChRs in PC12D cells activate endogenous Ca2+ 
      channels that are regulated independently of Ca2+ stores and require the 
      expression of TRPC6.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Neurochemistry, Faculty of Medicine, University of Tokyo, Hongo 
      7-3-1, Bunkyo-ku, Tokyo 113-0033.
FAU - Guo, Feifan
AU  - Guo F
FAU - Kim, Ju Young
AU  - Kim JY
FAU - Saffen, David
AU  - Saffen D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Biochem
JT  - Journal of biochemistry
JID - 0376600
RN  - 0 (Cholinergic Agonists)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (TRPC Cation Channels)
RN  - 0 (Trpc6 protein, rat)
RN  - 24GP945V5T (Barium)
RN  - 8Y164V895Y (Carbachol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Barium/metabolism
MH  - Calcium/*metabolism
MH  - Carbachol/pharmacology
MH  - Cholinergic Agonists/pharmacology
MH  - Ion Channel Gating/*drug effects
MH  - PC12 Cells
MH  - Rats
MH  - Receptors, Muscarinic/*physiology
MH  - TRPC Cation Channels/*metabolism
EDAT- 2006/03/29 09:00
MHDA- 2007/10/27 09:00
CRDT- 2006/03/29 09:00
PHST- 2006/03/29 09:00 [pubmed]
PHST- 2007/10/27 09:00 [medline]
PHST- 2006/03/29 09:00 [entrez]
AID - 139/3/459 [pii]
AID - 10.1093/jb/mvj065 [doi]
PST - ppublish
SO  - J Biochem. 2006 Mar;139(3):459-70. doi: 10.1093/jb/mvj065.