Dataset Information

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K⁺ current by different G-protein coupled receptors.

ABSTRACT:

Background and purpose

Elevated angiotensin II (Ang II) and sympathetic activity contributes to a high risk of ventricular arrhythmias in heart disease. The rapidly activating delayed rectifier K⁺ current (I_Kr ) carried by the hERG channels plays a critical role in cardiac repolarization, and decreased I_Kr is involved in increased cardiac arrhythmogenicity. Stimulation of α_1A -adrenoreceptors or angiotensin II AT₁ receptors is known to inhibit I_Kr via PKC. Here, we have identified the PKC isoenzymes mediating the inhibition of I_Kr by activation of these two different GPCRs.

Experimental approach

The whole-cell patch-clamp technique was used to record I_Kr in guinea pig cardiomyocytes and HEK293 cells co-transfected with hERG and α_1A -adrenoreceptor or AT₁ receptor genes.

Key results

A broad spectrum PKC inhibitor Gö6983 (not inhibiting PKCε), a selective cPKC inhibitor Gö6976 and a PKCα-specific inhibitor peptide, blocked the inhibition of I_Kr by the α_1A -adrenoreceptor agonist A61603. However, these inhibitors did not affect the reduction of I_Kr by activation of AT₁ receptors, whereas the PKCε-selective inhibitor peptide did block the effect. The effects of angiotensin II and the PKCε activator peptide were inhibited in mutant hERG channels in which 17 of the 18 PKC phosphorylation sites were deleted, whereas a deletion of the N-terminus of the hERG channels selectively prevented the inhibition elicited by A61603 and the cPKC activator peptide.

Conclusions and implications

Our results indicated that inhibition of I_Kr by activation of α_1A -adrenoreceptors or AT₁ receptors were mediated by PKCα and PKCε isoforms respectively, through different molecular mechanisms.

SUBMITTER: Liu X

PROVIDER: S-EPMC5715974 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Dataset Information

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K⁺ current by different G-protein coupled receptors.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K+ current by different G-protein coupled receptors.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Different protein kinase C isoenzymes mediate inhibition of cardiac rapidly activating delayed rectifier K⁺ current by different G-protein coupled receptors.