Background: Hydrogen peroxide (H2O2)-induced oxidative stress has been demonstrated to induce afterdepolarizations and triggered activities in isolated myocytes, but the underlying mechanisms remain not fully understood. We aimed to explore whether protein kinase C (PKC) activation plays an important
[...] Read more.
Background: Hydrogen peroxide (H
2O
2)-induced oxidative stress has been demonstrated to induce afterdepolarizations and triggered activities in isolated myocytes, but the underlying mechanisms remain not fully understood. We aimed to explore whether protein kinase C (PKC) activation plays an important role in oxidative stress-induced afterdepolarizations. Methods: Action potentials and ion currents of isolated rabbit cardiomyocytes were recorded using the patch clamp technique. H
2O
2 (1 mM) was perfused to induce oxidative stress and the specific classical PKC inhibitor, Gö 6983 (1 μM), was applied to test the involvement of PKC. Results: H
2O
2 perfusion prolonged the action potential duration and induced afterdepolarizations. Pretreatment with Gö 6983 prevented the emergence of H
2O
2-induced afterdepolarizations. Additional application of Gö 6983 with H
2O
2 effectively suppressed H
2O
2-induced afterdepolarizations. H
2O
2 increased the late sodium current (I
Na,L) (
n = 7,
p < 0.01) and the L-type calcium current (I
Ca,L) (
n = 5,
p < 0.01), which were significantly reversed by Gö 6983 (
p < 0.01). H
2O
2 also increased the transient outward potassium current (I
to) (
n = 6,
p < 0.05). However, Gö 6983 showed little effect on H
2O
2-induced enhancement of I
to. Conclusions: H
2O
2 induced afterdepolarizations via the activation of PKC and the enhancement of I
Ca,L and I
Na,L. These results provide evidence of a link between oxidative stress, PKC activation and afterdepolarizations.
Full article