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Functional interaction of Junctophilin 2 with small conductance Ca2+‐activated potassium channel subtype 2(SK2) in mouse cardiac myocytes

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Acta Physiologica

Published online on


Aim Junctophilins (JPs), a protein family of the junctional membrane complex, maintain the close conjunction between cell surface and intracellular membranes in striate muscle cells mediating the cross talk between extracellular Ca2+ entry and intracellular Ca2+ release. The small conductance Ca2+‐activated K+ channels are activated by the intracellular calcium and play an essential role in the cardiac action potential profile. Molecular mechanisms of regulation of the SK channels are still uncertain. Here we sought to determine whether there is a functional interaction of junctophilin type 2(JP2) with the SK channels and whether JP2 gene silencing might modulate the SK channels function in cardiac myocytes. Methods Association of JP2 with SK2 channel in mouse heart tissue as well as HEK 293 cells was studied using in vivo and in vitro approaches. siRNA knockdown of JP2 gene was assessed by Real time PCR. The expression of proteins was analyzed by Western blotting. Ca2+‐activated K+ current (IK,Ca) in infected adult mouse cardiac myocytes was recorded using whole‐cell voltage‐clamp technique. The intracellular Ca2+ transient was measured using an IonOptix photometry system. Results We showed for the first time that JP2 associates with the SK2 channel in native cardiac tissue. JP2, via the Membrane Occupation and Recognition Nexus (MORN motifs) in its N terminus, directly interacted with SK2 channels. A co‐localization of the SK2 channel with its interaction protein of JP2 was found in the cardiac myocytes. Moreover, we demonstrated that JP2 is necessary for the proper cell‐surface expression of the SK2 channel in HEK293. Functional experiments indicated that knockdown of JP2 caused a significant decrease in the density of IK,Ca and reduced the amplitude of the Ca2+ transient in infected cardiomyocytes. Conclusions The present data provide evidence that the functional interaction between JP2 and SK2 channels is present in the native mouse heart tissue. Junctophilin 2, as junctional membrane complex (JMC)protein, is an important regulator of the cardiac SK channels. This article is protected by copyright. All rights reserved.