Drug profiling using planar microelectrode arrays.
Microelectrode arrays (MEAs) with evenly distributed multiple sensor spots have been designed for specific applications. Using the MEAs, we determined the relative profiles of potassium channel openers (KCOs) on cultured embryonic Sprague-Dawley rat cardiac myocytes. KCO, pinacidil (PIN), cromakalim (CROM), SDZ PCO400 (SDZ), or its vehicle, was added to the myocytes cumulatively. The action potential signal shapes in the presence of PIN and SDZ show that the changes in voltage over time and the magnitudes of the associated voltage change were reduced concentration-dependently. CROM affected sodium influx more than PIN and SDZ. The comparisons of changes in the rate of beating and propagation speed in the presence of KCOs were made using their corresponding pD(2) values (the negative log of EC(50)). All KCOs caused concentration-dependent reductions in the rate of beating and propagation speed, with SDZ being the most potent. In addition to the signal shapes, rate of beating, and propagation speed, the origin of excitation and the excitation pattern inside the culture can be also extracted. The results show that the present system can differentiate the effects of different KCOs on myocytes. It might be possible to utilise the MEA as a means to classify drug action based upon a combined interpretation of the three different datasets gained from the extracellular recordings. The combination of these observations might be used as 'drug signatures' when profiling drugs in the future.
Yeung
C K
CK
Electronic and Computer Engineering, The University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Sommerhage
F
F
Wrobel
G
G
Offenhäusser
A
A
Chan
M
M
Ingebrandt
S
S
D000818:Animals; D008839:Microelectrodes; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004364:Pharmaceutical Preparations