Cells on a chip--the use of electric properties for highly sensitive monitoring of blood-derived factors involved in angiotensin II type 1 receptor signalling.
BACKGROUND
We developed a highly sensitive cardiomyocyte based screening system for the non-destructive electronic detection of chronotropic drugs and tissue-secreted factors involved in AT1 receptor-mediated cardiovascular diseases.


METHODS
For this purpose we cultured spontaneously beating neonatal rat cardiomyocytes on microelectrode arrays (MEAs), and tested the optimised, stable culture parameters for a reproducible real-time recording of alterations in contraction frequency. After the evaluation of culture parameters, computer-based electronic measurement systems were used for counting of contractions by recording of the field potential of cardiomyocytes.


RESULTS
Using the biosensor, angiotensin II, the predominant ligand of the AT1 receptor, was detected at very low concentrations of 10(-11) M via altered contractions of cardiomyocytes. Moreover, we demonstrated that cardiomyocyte coupled microarrays allow the detection of blood-derived low concentrated anti-AT1 receptor autoimmune antibodies of pregnant women suffering from preeclampsia.


CONCLUSIONS
This study demonstrates the first well-suited electrophysiological recording of cardiomyocytes on multielectrode arrays as a benefit for functional biomonitoring for the detection of AT1 receptor/ligand interactions and other marker proteins in sera directed to cardiovascular diseases.
Rothermel
Andrée
A
Center for Biotechnology and Biomedicine, Department of Molecular biological- biochemical Processing Technology, University of Leipzig, Germany. andree.rothermel@bbz.uni-leipzig.de
Kurz
Randy
R
Rüffer
Markus
M
Weigel
Winnie
W
Jahnke
Heinz-Georg
HG
Sedello
Anna K
AK
Stepan
Holger
H
Faber
Renaldo
R
Schulze-Forster
Kai
K
Robitzki
Andrea A
AA
D000804:Angiotensin II / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000097:blood; D001483:Base Sequence; D015374:Biosensing Techniques / Q000379:methods* / Q000706:statistics & numerical data; D018914:Cells, Immobilized; D004594:Electrophysiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000276:immunology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D001323:Autoantibodies; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II