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- W2063722771 abstract "Voltage gated ion channels (VGICs) play crucial roles in the propagation electrical signals in excitable cells. In contrast, several VGICs have been also known to express in non-excitable cells and participate in keeping cell homeostasis. The voltage-gated potassium channel subfamily A member 3 (Kv1.3) is one of the Shaker-related channels expressed mainly on T lymphocytes. Many reports have indicated that Kv1.3 is associated with several diseases including autoimmune diseases, inflammatory diseases and obesity. On the other hand, the voltage-gated sodium channel (Nav) Beta 1 is known as a subunit modulating kinetics and expression of Nav, but several studies have shown that NavBeta1 also participates in brain development and cell signaling. These ‘non-canonical’ functions in VGICs have been focused upon recently and an exciting report showed the functional interaction between murine Kv1.3 (mKv1.3) and rat Navbeta1 (rBeta1) (Nguyan HM et al. PNAS 2012). The authors demonstrated that the activation of mKv1.3 ionic current is accelerated by rBeta1. Here, we explore the molecular mechanisms of the acceleration in Kv1.3 activation through gating currents of human Kv1.3 (hKv1.3) with and without rBeta1 using the cut-open voltage clamp technique. We found that the N-terminus of hKv1.3 is associated with trafficking efficiency of the protein to the membrane in Xenopus oocytes. Our data indicated that rBeta1 did not accelerate the gating current activation of hKv1.3, but shifted the Q-V in the depolarizing direction and slowed their kinetics. Because there are several differences in the amino acid sequences of mKv1.3 and hKv1.3, the differences between the previous report and our results may give clues on the molecular mechanisms of the functional interaction between Kv1.3 and rBeta1. Support: 13POST14800031 (AHA), U54GM087519 and R01GM030376" @default.
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- W2063722771 date "2015-01-01" @default.
- W2063722771 modified "2023-09-26" @default.
- W2063722771 title "Exploring Molecular Mechanisms of the Functional Interaction between Kv1.3 and Nav Beta1" @default.
- W2063722771 doi "https://doi.org/10.1016/j.bpj.2014.11.1527" @default.
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