PMID- 30261922
OWN - NLM
STAT- MEDLINE
DCOM- 20181102
LR  - 20240313
IS  - 1756-0500 (Electronic)
IS  - 1756-0500 (Linking)
VI  - 11
IP  - 1
DP  - 2018 Sep 27
TI  - Modulation of Ca(V)1.3b L-type calcium channels by M(1) muscarinic receptors 
      varies with Ca(V)beta subunit expression.
PG  - 681
LID - 10.1186/s13104-018-3783-x [doi]
LID - 681
AB  - OBJECTIVES: We examined whether two G protein-coupled receptors (GPCRs), 
      muscarinic M(1) receptors (M(1)Rs) and dopaminergic D(2) receptors (D(2)Rs), 
      utilize endogenously released fatty acid to inhibit L-type Ca(2+) channels, 
      Ca(V)1.3. HEK-293 cells, stably transfected with M(1)Rs, were used to transiently 
      transfect D(2)Rs and Ca(V)1.3b with different Ca(V)beta-subunits, allowing for 
      whole-cell current measurement from a pure channel population. RESULTS: M(1)R 
      activation with Oxotremorine-M inhibited currents from Ca(V)1.3b coexpressed with 
      alpha(2)delta-1 and a beta(1b), beta(2a), beta(3), or beta(4)-subunit. Surprisingly, the magnitude of 
      inhibition was less with beta(2a) than with other Ca(V)beta-subunits. Normalizing 
      currents revealed kinetic changes after modulation with beta(1b), beta(3), or beta(4), but 
      not beta(2a)-containing channels. We then examined if D(2)Rs modulate Ca(V)1.3b when 
      expressed with different Ca(V)beta-subunits. Stimulation with quinpirole produced 
      little inhibition or kinetic changes for Ca(V)1.3b coexpressed with beta(2a) or 
      beta(3). However, quinpirole inhibited N-type Ca(2+) currents in a 
      concentration-dependent manner, indicating functional expression of D(2)Rs. 
      N-current inhibition by quinpirole was voltage-dependent and independent of 
      phospholipase A(2) (PLA(2)), whereas a PLA(2) antagonist abolished M(1)R-mediated 
      N-current inhibition. These findings highlight the specific regulation of Ca(2+) 
      channels by different GPCRs. Moreover, tissue-specific and/or cellular 
      localization of Ca(V)1.3b with different Ca(V)beta-subunits could fine tune the 
      response of Ca(2+) influx following GPCR activation.
FAU - Roberts-Crowley, Mandy L
AU  - Roberts-Crowley ML
AD  - Department of Physiology, Program in Neuroscience, University of Massachusetts 
      Medical School, 55 Lake Ave North, Worcester, MA, 01655, USA.
FAU - Rittenhouse, Ann R
AU  - Rittenhouse AR
AUID- ORCID: 0000-0002-7446-230X
AD  - Department of Physiology, Program in Neuroscience, University of Massachusetts 
      Medical School, 55 Lake Ave North, Worcester, MA, 01655, USA. 
      Ann.Rittenhouse@umassmed.edu.
AD  - Department of Microbiology and Physiological Systems, Program in Neuroscience, 
      University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 
      01605, USA. Ann.Rittenhouse@umassmed.edu.
LA  - eng
GR  - R29 NS034195/NS/NINDS NIH HHS/United States
GR  - R01 NS034195/NS/NINDS NIH HHS/United States
GR  - T32 NS007366/NS/NINDS NIH HHS/United States
GR  - NS-34195/NS/NINDS NIH HHS/United States
GR  - TS-NS07366-09/NH/NIH HHS/United States
PT  - Journal Article
DEP - 20180927
PL  - England
TA  - BMC Res Notes
JT  - BMC research notes
JID - 101462768
RN  - 0 (CACNA1D protein, human)
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (Receptor, Muscarinic M1)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium
MH  - Calcium Channels, L-Type/*physiology
MH  - HEK293 Cells
MH  - Humans
MH  - Receptor, Muscarinic M1/*physiology
MH  - Receptors, Dopamine D2
MH  - Receptors, G-Protein-Coupled/*physiology
PMC - PMC6161362
OTO - NOTNLM
OT  - Acetylcholine
OT  - CaVbeta subunit
OT  - Dopamine
OT  - L-type calcium current
EDAT- 2018/09/29 06:00
MHDA- 2018/11/06 06:00
PMCR- 2018/09/27
CRDT- 2018/09/29 06:00
PHST- 2018/07/31 00:00 [received]
PHST- 2018/09/20 00:00 [accepted]
PHST- 2018/09/29 06:00 [entrez]
PHST- 2018/09/29 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/09/27 00:00 [pmc-release]
AID - 10.1186/s13104-018-3783-x [pii]
AID - 3783 [pii]
AID - 10.1186/s13104-018-3783-x [doi]
PST - epublish
SO  - BMC Res Notes. 2018 Sep 27;11(1):681. doi: 10.1186/s13104-018-3783-x.