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Pflügers Archiv

, Volume 439, Issue 6, pp 808–813 | Cite as

Effect of anoxic preconditioning on ATP-sensitive potassium channels in guinea-pig ventricular myocytes

  • Z. Zhu
  • Y.-L. Li
  • D.-P. Li
  • R.-R. He
Original Article

Abstract

Ischemic or hypoxic preconditioning in experimental animals and humans is described. The mechanism of preconditioning may involve several endogenous substances released from ischemic or hypoxic tissues (such as adenosine, noradrenaline and bradykinin) that stimulate protein kinase C (PKC), which then phosphorylates ATP-sensitive potassium channels (KATP channels). However, the effect of hypoxic preconditioning on KATP channels in guinea-pig ventricular myocytes is unclear. The uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) has been shown to activate KATP channels in isolated cardiac cells. In the present study we tested whether anoxic preconditioning (APC) could affect the opening of KATP channels activated by metabolic inhibition (MI) induced by FCCP in cell-attached and inside-out patches from guinea-pig ventricular myocytes. We measured the channel activity as NP o i and calculated it using the formula P o=I/(Ni), where P o is open-state probability, I is the mean patch current carried by all KATP channels activated in a particular patch for a certain period of time, N is the number of functioning channels in the patch, and i is the unitary current of the KATP channels. In cell-attached membrane patches, after about 5 min of initiating MI, KATP channels were activated at a holding potential of +40 mV (NP o i=3.7±0.9 pA); APC pretreatment (3 min of anoxia followed by 7 min of reoxygenation) before MI (APC+MI group) shortened the time to activate KATP channels by MI (2.3±0.5 min) and increased the activity of KATP currents (NP o i=8.4±0.5 pA). This effect of APC was eliminated by administration of a PKC blocker, chelerythrine (5 µM), for 5 min before the APC pretreatment. In the inside-out patches, the IC50 of intracellular ATP against the KATP channels in the APC+MI group was significantly increased to 642 µM compared to that in the MI group (IC50 of intracellular ATP =252 µM). Chelerythrine inhibited the effect of APC on the sensitivity of KATP channels to the intracellular ATP concentration (IC50 of [ATP]i=301 µM). Our results demonstrate that APC can increase and accelerate the opening of KATP channels induced by MI, and decrease the sensitivity of KATP channels to [ATP]i, which is mediated by promoting the activation of PKC induced by APC.

Anoxic preconditioning ATP-sensitive K+ channels Cardiomyocytes Metabolic inhibition Protein kinase C 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Z. Zhu
    • 1
  • Y.-L. Li
    • 1
  • D.-P. Li
    • 1
  • R.-R. He
    • 1
  1. 1.Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017People's Republic of China

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