Specific protein kinase C isoform exerts chronic inhibition on the slowly activating delayed-rectifier potassium current by affecting channel trafficking.

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 24Ā hours). Further evidence showed that PKCĪµ knockdown by siRNA antagonized the AngII-induced chronic inhibition on the I Ks current, whereas knockdown of cPKC (PKCĪ± and PKCĪ²) 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 PKCĪµ 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. PMID: 33535882 [PubMed - in process]
Source: Channels - Category: Molecular Biology Tags: Channels (Austin) Source Type: research