Key Points
- To determine whether and how protein kinase C activates ATP-sensitive potassium currents in rabbit and human ventricular myocytes.
- Isolated rabbit and human ventricular myocytes were dialyzed with varying pipette ATP concentrations while minimizing sodium and calcium currents.
- Myocytes were exposed to the protein kinase C activator phorbol 12,13-didecanoate (PDD), the inactive analogue 4-alpha-PDD under blinded conditions, and the selective inhibitor bisindolylmaleimide.
- In rabbit myocytes, PDD activated ATP-sensitive potassium currents concentration-dependently (EC50 7.1 nmol/L) and shifted the ATP EC50 from 260 to 601 µmol/L; 1 µmol/L PDD elicited currents in 8 of 9 cells compared to 0 of 5 cells for 4-alpha-PDD (P = .003), an effect completely prevented by bisindolylmaleimide.
- In human myocytes, 0.1 µmol/L PDD induced currents in 5 of 5 cells at 100 µmol/L ATP and 5 of 5 cells at 400 µmol/L ATP, but failed to elicit currents in 0 of 5 cells at 1 mmol/L ATP.
Structured PICO
PPopulationRabbit and human ventricular myocytes
IInterventionPhorbol 12,13-didecanoate (PDD) superfusion (0.1 to 1 micromol/L)
CComparatorControl conditions, non-PKC-stimulating analogue 4 alpha-PDD, or PKC inhibitor bisindolylmaleimide
OOutcomeActivation of ATP-sensitive K+ current (I(KATP))surrogate
Protein kinase C activates ATP-sensitive K+ channels in human and rabbit ventricular myocytes by reducing channel sensitivity to intracellular ATP, providing a potential mechanistic link for ischemic preconditioning.