A study of the relationship between pharmacologic preconditioning and adenosine triphosphate-sensitive potassium (KATP) channels on cultured cardiomyocytes using the microelectrode array.
The microelectrode array was used to study the pharmacologic preconditioning effect of adenosine triphosphate-sensitive channel activation using potassium channel openers (KCOs) on rat cardiomyocytes over 90 minutes of ischemia. Cell viability and electrophysiological changes between KCOs pretreated and untreated cardiomyocytes were compared. Ischemia caused significant increases in beat frequency, extracellular field potential amplitude, and propagation velocity of spontaneously beating untreated cardiomyocytes. However, these electrophysiological parameters reduced as the duration of ischemia increased. The electrophysiological changes on ischemic cardiomyocytes were abolished by pretreating the cells with KCOs. Pinacidil pretreated cardiomyocytes retained a significantly higher viability than the untreated cardiomyocytes after 90 minutes of ischemia. Because Connexin 43 has a direct correlation with the propagation velocity, the Connexin 43 protein expression was also investigated. Connexin 43 expression levels were lower in KCOs pretreated cardiomyocytes than that of the untreated controls, and this correlated with the propagation velocity results obtained from the microelectrode array. The effect of pinacidil (sarcolemmal adenosine triphosphate-sensitive channel opener) was more prominent than that of diazoxide (mitochondrial K adenosine triphosphate-sensitive channel opener) on ischemic cardiomyocytes as indicated in the present acute ischemia study.
Law
Jessica Ka-Yan
JK
Bioengineering Graduate Program, The Hong Kong University of Science and Technology (HKUST), Clear Water Bay, Hong Kong.
Yeung
Chi-Kong
CK
Yiu
Ka-Lap
KL
Rudd
John Anthony
JA
Ingebrandt
Sven
S
Chan
Mansun
M
D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics; D003981:Diazoxide / Q000494:pharmacology; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D008839:Microelectrodes; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D018031:Connexin 43; D054086:KATP Channels; D015221:Potassium Channels; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D020110:Pinacidil; D003981:Diazoxide