Blockade of myocardial ATP-sensitive potassium channels by ketamine.
BACKGROUND
The adenosine triphosphate (ATP)-sensitive potassium (KATP) channel underlies the increase in potassium permeability during hypoxia and ischemia. The increased outward potassium current during ischemia may be an endogenous cardioprotective mechanism. This study was designed to determine the effects of ketamine on KATP channel in rat hearts.


METHODS
Inside-out and cell-attached configurations of patch-clamp techniques and 3 M potassium chloride-filled conventional microelectrodes were used to investigate the effect of ketamine on KATP channel currents in single rat ventricular myocytes and on the action potential duration of rat papillary muscles, respectively.


RESULTS
Ketamine inhibited KATP channel activity in rat ventricular myocytes in a concentration-dependent manner. In the inside-out patches, the concentration of ketamine for half-maximal inhibition and the Hill coefficient were 62.9 microM and 0.54, respectively. In a concentration-dependent manner, ketamine inhibited pinacidil- and 2,4-dinitrophenol-activated KATP channels in cell-attached patches. The application of ketamine to the intracellular side of membrane patches did not affect the conduction of single-channel currents of KATP channels. Ketamine increased the action potential duration, which was then shortened by pinacidil in a concentration-dependent manner.


CONCLUSIONS
Ketamine inhibited KATP channel activity in a concentration-dependent manner. These results suggest that ketamine may attenuate the cardioprotective effects of the KATP channel during ischemia and reperfusion in the rat myocardium.
Ko
S H
SH
Chonbuk National University Medical School, Keum-Am Dong Chonju, Korea.
Lee
S K
SK
Han
Y J
YJ
Choe
H
H
Kwak
Y G
YG
Chae
S W
SW
Cho
K P
KP
Song
H S
HS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000778:Anesthetics, Dissociative; D015221:Potassium Channels; D007649:Ketamine; D000255:Adenosine Triphosphate