Introduction of KCNK16
KCNK16, the full name is potassium channel subfamily K member 16, also known as 2P domain potassium channel Talk-1, TWIK-related alkaline pH-activated K(+) channel 1 (TALK-1). KCNK16, which codes for the TALK-1 channel, is the most abundant K+ channel transcript found in human pancreatic islets β-cells. The secondary structure of TALK-1 contains four transmembrane domains, two extracellular loops, and intracellular N- and C-termini. There are four human TALK-1 transcript variants, including two that form functional K+ channels: TALK-1a (transcript variant 2 (T2)) and TALK1-b (transcript variant 3 (T3)). Similar to several other K2P channels, TALK-1 is sensitive to pH, and it increases activity under alkaline conditions, while decreases activity under acidic conditions.
|Basic Information of KCNK16|
|Protein Name||Potassium channel subfamily K member 16|
|Aliases||2P domain potassium channel Talk-1, TWIK-related alkaline pH-activated K(+) channel 1 (TALK-1)|
|Organism||Homo sapiens (Human)|
Function of KCNK16 Membrane Protein
The TALK-1 K+ channel regulates beta cell electrical excitability by polarizing beta cell membrane potential (Vm). Islet beta cells from TALK-1 knockout (KO) mice showed increased Vm depolarization, increased Ca2+ influx and elevated second phase glucose-stimulated insulin secretion (GSIS). In addition, non-synonymous polymorphisms in TALK-1 (rs1535500) resulted in the replacement of 277 alanine (A) with glutamate (E), which is associated with an increased risk of type 2 diabetes. This polymorphism leads to a gain-of-function (GOF) of TALK-1 channel that increases its open probability, predicts its hyperpolarized beta cell Vm and decreases Ca2+ influx and insulin secretion.
Fig.1 Dendrogram of 2P domain K+ channels.
Application of KCNK16 Membrane Protein in Literature
These data indicated that TALK-1 reduced cytosolic Ca2+ elevations of δ-cell and somatostatin released by limiting δ-cell Ca2+-induced Ca2+ release (CICR), modulating the intraislet paracrine signaling mechanisms that controlled glucagon secretion.
The data herein established TALK-1 channel as a key regulator of ER Ca(2+) in β-cells, and suggested that TALK-1 may be a therapeutic target for reducing ER Ca(2+) treatment defected in β-cells during the pathogenesis of diabetes.
The TALK-1/iOPN complex caused Vm hyperpolarization and reduced β-cell glucose-stimulated Ca2+ influx, which is predicted to inhibit glucose-stimulated insulin secretion (GSIS).
These findings revealed the TALK-1 channel as an important regulator of second-stage insulin secretion and suggested a clinically relevant mechanism for rs1535500 that increased the risk of type 2 diabetes by limiting glucose-stimulated insulin secretion.
It had been discovered herein that at least two functional TALK-1 variants were present and could be used as background K+ currents in certain cells of the human pancreas.
KCNK16 Preparation Options
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