Specific protein kinase C isoform exerts chronic inhibition on the slowly activating delayed-rectifier potassium current by affecting channel trafficking. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Gou, Xiangbo; Hu, Tingting; Gou, Yu; Li, Chaoqi; Yi, Ming; Jia, Mengran
• Is Part Of: Channels. Volume 15:Issue 1(2021)
• Page Start: 262
• Page End: 272
• Publication Date: 2021-01-01
• Subjects: Protein kinase C -- ion channel -- Iks -- KCNQ1 -- intracellular trafficking; Ion channels -- Periodicals; 572.3
• DOI: 10.1080/19336950.2021.1882112
• Languages: English
• ISSNs: 1933-6950

Abstract

ABSTRACT: The slowly activating delayed rectifier K + current ( I Ks ) 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 I Ks 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 I Ks current. The I Ks 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 I Ks 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 I Ks 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 I Ks current, while the channel endocytosis inhibition with dynasore alleviated both Ang II and PMA-induced chronic inhibition on I Ks 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.