KCNE1

KCNE1 gene provides instructions for the synthesis of proteins that regulate the activity of potassium channels. These channels transport positively charged potassium ions into and out of the cell, and play a key role in the cell's ability to generate and transmit electrical signals. Existing studies have found that the specific function of potassium ion channels depends on its composition and location in the body. Among them, KCNE1 protein participates in the formation of a potassium channel composed of four subunits. The KCNQ1 gene encodes the α subunit, and the KCNE1 gene produces the β subunit. The β subunit participates in channel formation and plays a function of regulating channel activity. Clinical studies have shown that these channels are active in the inner ear and heart muscle, where they transport potassium ions out of the cell. In the inner ear, these channels play a role in maintaining the proper ion balance required for normal hearing. In the heart, these channels are involved in charging the heart muscle after each heartbeat to maintain a regular rhythm. In addition, KCNE1 protein is also produced in the kidneys, testes and uterus, and it may regulate the activity of other channels.

Figure 1. KCNE1 can serve as an auxiliary subunit of two superfamilies of ion channels.(PabloÁvalos Prado, et al.; 2021)

Cloning and Expression of KCNE1

Potassium ion channels are essential for many cell functions in excitable and non-excitable cells, and show a high degree of diversity, with different electrophysiological and pharmacological properties. Through molecular cloning and sequence analysis of its genomic DNA, scientists inferred the amino acid sequence of a new type of human membrane protein that induces selective potassium permeation through membrane depolarization. The protein consists of 129 amino acid residues and has structural features similar to those of rats. The transmembrane domain and its flanking c-terminal sequences are highly conserved between human and rat sequences. The slow activation of potassium current expression in Xenopus oocytes by human protein is not significantly different from the potassium current induced by rat protein. Through genome sequence analysis, the researchers found that the KCNE1 gene contains 3 exons and 2 introns located in the 5-prime untranslated region. Through somatic cell hybridization and isotope in situ hybridization, it was determined that the KCNE1 gene is located at 21q22.1-q22.2.

KCNE1 and Disease

Jervell and Lange-Nielsen Syndrome

Clinical studies have found that at least four mutations in the KCNE1 gene have been found in patients with Jervell and lge-nielsen syndrome, which can cause arrhythmia and severe hearing loss from birth. About 10% of cases are caused by this gene mutation. Affected people usually have mutations in both copies of the KCNE1 gene in each cell. These mutations changed a single amino acid sequence in the KCNE1 protein, thereby disrupting the normal structure of the protein. The mutant KCNE1 protein cannot regulate the flow of potassium ions through the inner ear and myocardial channels. This loss of channel function leads to arrhythmias and hearing loss characteristic of Jervell and lge-nielsen syndrome.

Other disorders

Certain medications, including those used to treat arrhythmias, infections, epilepsy, and psychosis, may cause abnormal heart rhythms in some people. The heart disease caused by this drug, known as Acquired Long QT Syndrome, increases the risk of cardiac arrest and sudden death. A small number of acquired long QT syndromes occur in people with potential mutations in the KCNE1 gene.

References

1. Abbott GW. KCNE1 and KCNE3: The yin and yang of voltage-gated K(+) channel regulation. Gene. 2016, 576(1 Pt 1):1-13.
2. Chan PJ, et al.; Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. J Gen Physiol. 2012, 139(2):135-44.
3. Ehmke H. Physiological functions of the regulatory potassium channel subunit KCNE1. Am J Physiol Regul Integr Comp Physiol. 2002, 282(3):R637-8.
4. Lundquist AL, et al.; Expression and transcriptional control of human KCNE genes. Genomics. 2006, 87(1):119-28.
5. Melman YF, et al.; KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity. Neuron. 2004, 42(6):927-37.
6. Murai, T., et al.; Molecular cloning and sequence analysis of human genomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity. Biochem. Biophys. Res. Commun. 1989,161: 176-181.
7. Splawski, I., et al.; Mutations in the hminK gene cause long QT syndrome and suppress I(Ks) function. Nature Genet. 1997, 17: 338-340.
8. PabloÁvalos Prado, et al.; KCNE1 is an auxiliary subunit of two distinct ion channel superfamilies. Cell. 2021, 184, 534-544.