Preconditioning with PKC and the ATP-sensitive potassium channels: a codependent relationship.
BACKGROUND
Both potassium channel openers and protein kinase C have been shown to independently elicit the myoprotective preconditioning response. However, the in vivo dependency between the two is unknown.


METHODS
Thirty-seven sheep were divided into seven groups; animals received no pretreatment, pinacidil, pinacidil and potassium channel opener blocker glibenclamide, protein kinase C activator 4beta-phorbol-12,13-dibutyrate (PDBu), or PDBu and protein kinase C blocker chelerythrine. The last two groups underwent opposite blockade, chelerythrine + pinacidil, or glibenclamide + PDBu. All groups underwent 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Regional function was assessed throughout the experiment, and at the conclusion of the study the infarct size (as a percentage of the area at risk) was determined.


RESULTS
Infarct size decreased in the groups receiving only pinacidil or PDBu (control: 54%+/-3%, pinacidil: 25% +/-2%, PDBu: 21%+/-3%; p<0.05 pinacidil or PDBu versus control). This preconditioning protection was lost when the direct blocker was given (58%+/-5%, glibenclamide + pinacidil; 70%+/-6%, chelerythrine + PDBu; p = not significant versus control). The preconditioning response was again attenuated when the opposite blockers were given (64%+/-5%, chelerythrine + pinacidil; 63%+/-1%, glibenclamide + PDBu; p = not significant versus control). There was no significant difference in regional function.


CONCLUSIONS
This study shows that both protein kinase C and potassium channels are necessary and codependent for preconditioning in the in vivo heart.
Gaudette
G R
GR
Division of Cardiothoracic Surgery, University Hospital at Stony Brook and the State University of New York, USA.
Krukenkamp
I B
IB
Saltman
A E
AE
Horimoto
H
H
Levitsky
S
S
D000818:Animals; D001835:Body Weight; D005260:Female; D006339:Heart Rate; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D015221:Potassium Channels; D014665:Vasodilator Agents; D020110:Pinacidil; D011493:Protein Kinase C