Involvement of Caveolin in Low K+-induced Endocytic Degradation of Cell-surface Human Ether-a-go-go-related Gene (hERG) Channels

The Serum- and Glucocorticoid-inducible Kinases SGK1 and SGK3 Regulate hERG Channel Expression via Ubiquitin Ligase Nedd4-2 and GTPase Rab11

“…For instance, a decrease in extracellular potassium concentration clinically known as hypokalemia has been found to induce hERG internalization from the plasma membrane (7). Internalization of cell surface hERG channels occurs through a caveolin-dependent pathway (8). Caveolae are plasma membrane pits that form stable membrane domains and function as carriers in the endocytic pathway (9).…”

Phenotypic Correlation of Genetic Mutations with Ventricular Arrhythmias

“…Recently, the work of Guo and colleagues has provided a biochemical basis and mechanistic approach to study the behavior of HERG in low-potassium conditions. The 155 kDa form of HERG undergoes endocytic internalization from the plasma membrane and proteasomal degradation through a mechanism involving caveolin (Massaeli et al, 2010). Further work was done by Massaeli and colleagues who studied the behavior of pore-lining mutations in HERG under zero-potassium conditions.…”

To Be or Not to Be

“…8 In addition, caveolins are involved in low K + o -induced degradation of mature IKr channels. 9 Although these data suggest plausible mechanisms for LQTS in individuals with CAV3 mutations, the clinical data supporting CAV3 mutations as pathogenic, particularly T78M, are sparse. In Vatta et al's initial report, 1 T78M was seen in 3 patients, 1 of whom had a concomitant known LQT2 mutation.…”