Ratiometric calcium measurement

From: Beth Whalen (BWhalen@prl.pulmonary.ubc.ca)
Date: Fri Jun 18 1999 - 13:30:25 EST


Hello,

I recently posted a question about calcium measurement.  I 
received a couple of helpful responses but received many more 
responses from people wanting to know what I found out.  He it is: 


Dear Beth,

We have been using the fluo-3/fura red method for a couple of 
years here and
it works very successfully:

In response to your specific questions:

*	
We use the Coulter XL measuring Fluo 3 emission in the FL1 
detector
and Fura red in the FL4 detector.
*	
Because we analyse lymphocyte activation with both antibody
stimulation and using peptide pulsed B cells I trigger on FL4 thus 
excluding
non-loaded cells from the analysis.

Here is a brief method:

Cells were suspended in 30mM HEPES buffered RPMI and loaded 
with 3mM Fluo
3-AM and 8mM Fura red-AM (Molecular Probes Europe, 
Netherlands) in the
presence of pluronic F127 detergent (Sigma , UK, final 
concentration 0.05%)
for 30 minutes at 37*C.  Cells were then washed and re-suspended 
at 5x105/ml
and warmed to 37*C for 10 minutes prior to use.  Calcium flux was 
measured
using a Coulter XL MCL flow cytometer (Coulter, USA).  Mean ratio 
of Fluo
3/Fura red fluorescence was measured during the acquisition time 
course and
expressed grapically to indicate calcium flux.

*	
The method is better than Fluo-3 alone since a ratiometric 
technique
renders the data independent of dye loading, cell size, dye leakage 
and
photobleaching.  The low noise and high sensitivity are comparable 
to indo-1
at the ranges of calcium concentrations found in T cells.

Regards,

Simon



Beth,
We use a 3-color FacsCalibur with a 488 nm laser.  I use 
Fluo3/Fura Red or
(better) Fluo4/Fura Red to measure calcium mobilization in B cells 
(J.
Immunol. 162:2717). I also helped another lab here use Fluo3/Fura 
Red in
human PMNs with very good results. Fluo3 alone is less sensitive 
and less
consistent than Fluo3+ Fura Red as a calcium indicator.  
Computing the
ratio of fluorescence from 2 dyes allows you to correct for cell to 
cell
variability in dye loading.
Good luck
Lynn Dustin


Hi Beth,

Yes the ratiometric method is much better.  Using just Fluo-3 the 
intensity of signal is dependent on the loading efficiency, so if you 
are comparing several cell preps they may be all different.  If you 
use the ratio your measurement is no longer affected by loading 
efficiency and also the difference between resting and full deflection 
will be greater as the fura-red signal gets less as your fluo gets 
greater.  I found it works better if you use FL3 to collect your Fura-
red.  You can use FACS Assistant to get the ratio and export the 
data file, then look at using a graph making program like cricket 
graph (plots look pretty cool you can smooth them if they are too 
spiky).  When you are loading you can add both dyes at the same 
time so it doesn't take any longer.  We ppublished some work a 
while back in J.Exp Med 188 pp2057-65, I think we put our protocol 
in there somewhere.

Simon Monard
ADARC
NYC


Thank you for you comments.

Beth Whalen
U.B.C. Pulmonary Research Lab.
St. Paul's Hospital
Vancouver, B.C.



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