Na-K-2Cl Cotransporter and Store-Operated Ca²⁺ Entry in Pacemaking by Interstitial Cells of Cajal.

ABSTRACT: Pacemaker depolarization in interstitial cells of Cajal (ICCs) is believed to be induced by Ca²⁺ transients and activation of anoctamin-1 (Ano1) channels in the plasma membrane. However, block of store-operated calcium entry (SOCE) or the Na-K-2Cl cotransporter (NKCC1) terminates pacemaker activity in ICC, indicating these transporters are involved in the initiation or maintenance of pacemaker activity. We hypothesized that SOCE contributes to pacemaker depolarization by maintaining [Ca²⁺] in the endoplasmic reticulum, which is the underlying source of Ca²⁺ transients for activation of Ano1. NKCC1 maintains the Cl^- gradient supporting the driving force for inward current mediated by Ano1. Currently mechanisms sustaining release of Ca²⁺

SUBMITTER: Youm JB 

PROVIDER: S-EPMC6713646 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature