Functional KV10.1 Channels Localize to the Inner Nuclear Membrane

Abstract

Ectopically expressed human KV10.1 channels are relevant players in tumor biology. However, their function as ion channels at the plasma membrane does not totally explain their crucial role in tumors. Both in native and heterologous systems, it has been observed that a majority of KV10.1 channels remain at intracellular locations. In this study we investigated the localization and possible roles of perinuclear KV10.1. We show that KV10.1 is expressed at the inner nuclear membrane in both human and rat models; it co-purifies with established inner nuclear membrane markers, shows resistance to detergent extraction and restricted mobility, all of them typical features of proteins at the inner nuclear membrane. KV10.1 channels at the inner nuclear membrane are not all transported directly from the ER but rather have been exposed to the extracellular milieu. Patch clamp experiments on nuclei devoid of external nuclear membrane reveal the existence of channel activity compatible with KV10.1. We hypothesize that KV10.1 channels at the nuclear envelope might participate in the homeostasis of nuclear K+, or indirectly interact with heterochromatin, both factors known to affect gene expression.

Overexpression of potassium channel ether à go-go in human osteosarcoma

“…5). While hEAG1 is definitely a transmembrane protein, previous studies have reported similar findings that immunostaining of hEAG1 is preferentially cytoplasmic with predominant perinuclear localization (7,19), perhaps due to the functional hEAG1 localizes to the inner nuclear membrance (20). Taken together, these data prove that we have generated hEAG1 polyclonal antibody with high activity and specificity, which could be used for further characterization of hEAG1 expression patterns and function.…”

Nuclear Localization and Functional Characteristics of Voltage-gated Potassium Channel Kv1.3

“…Nuclear Kv channel immunoreactivity has also been reported in the paraventricular nucleus projecting into the rostral ventrolateral medulla (33). Recently, eag I channels were found to be localized on the nuclear membrane of Kv10.1-transfected cells, MCF7 cells, and rat cerebellum and hippocampus (34). Interestingly, Mazzanti et al (35) suggested that nuclear pores may be K ϩ selective and that K ϩ channels might form part of the nuclear pore, which provides a conductive pathway between nuclear membranes.…”

KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone

“…KCNH1 channel activity has been proposed to provide the hyperpolarising current required in myoblasts just before cell fusion (Occhiodoro et al 1998). A nuclear localisation sequence is present in KCNH1 and potassium currents resembling Kcnh1 channel activity blocked by astemizole have been reported in the nuclear membrane (Chen et al 2011). However, the potential role of KCNH1 in the nucleus remains elusive.…”