Specific Protein Kinase C Isoform Exerts Chronic Inhibition on the Slowly Activating Delayed-rectifier Potassium Current by Affecting Channel Trafficking

Overview

Journal Channels (Austin)

Specialty Biochemistry

Date 2021 Feb 4

PMID 33535882

Citations 3

Authors

Xiangbo Gou

Tingting Hu

Yu Gou

Chaoqi Li

Ming Yi

Mengran Jia

Affiliations

Soon will be listed here.

Abstract

The slowly activating delayed rectifier K current () plays a key role in the repolarization of ventricular action potential in the human heart and is formed by the pore-forming α-subunit encoded by KCNQ1 (Kv7.1) and β-subunit encoded by KCNE1. Evidence suggested that was regulated through protein kinase C (PKC) pathway, but the mechanism is controversial. This study was designed to identify the specific PKC isoform involved in the long-term regulation of current. The current was recorded using whole-cell patch-clamp technique in human embryonic kidney (HEK) 293B cell co-transfected with human KCNQ1/KCNE1 genes. The results revealed that both chronic activation of Ang II and PMA reduced the current in a long-term regulation (about 24 hours). Further evidence showed that PKCε knockdown by siRNA antagonized the AngII-induced chronic inhibition on the current, whereas knockdown of cPKC (PKCα and PKCβ) attenuated the inhibition effect of PMA on the current. Moreover, the forward transport inhibition of the channel with brefeldin A alleviated the Ang II-induced chronic inhibition on current, while the channel endocytosis inhibition with dynasore alleviated both Ang II and PMA-induced chronic inhibition on current. The above results showed that PKCε activation promoted the channel endocytosis and inhibited the channel forward transport to the plasma membrane, while cPKC activation only promoted the channel endocytosis, which both down regulated the channel current.

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