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Subcellular localization of the delayed rectifier K⁺ channels KCNQ1 and ERG1 in the rat heart

¹Department of Medical Physiology and Copenhagen Heart Research Center, and ²Institute of Medical Anatomy, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark; ³Institute of Biochemical Pharmacology, University of Innsbruck, A-6020 Innsbruck, Austria; and ⁴Division of Ion Channel Pharmacology, NeuroSearch, DK-2750 Ballerup, Denmark

Submitted 11 April 2003 ; accepted in final form 3 December 2003

In the heart, several K⁺ channels are responsible for the repolarization of the cardiac action potential, including transient outward and delayed rectifier K⁺ currents. In the present study, the cellular and subcellular localization of the two delayed rectifier K⁺ channels, KCNQ1 and ether-a-go-go-related gene-1 (ERG1), was investigated in the adult rat heart. Confocal immunofluorescence microscopy of atrial and ventricular cells revealed that whereas KCNQ1 labeling was detected in both the peripheral sarcolemma and a structure transversing the myocytes, ERG1 immunoreactivity was confined to the latter. Immunoelectron microscopy of atrial and ventricular myocytes showed that the ERG1 channel was primarily expressed in the transverse tubular system and its entrance, whereas KCNQ1 was detected in both the peripheral sarcolemma and in the T tubules. Thus, whereas ERG1 displays a very restricted subcellular localization pattern, KCNQ1 is more widely distributed within the cardiac cells. The localization of these K⁺ channels to the transverse tubular system close to the Ca²⁺ channels renders them with maximal repolarizing effect.

immunohistochemistry; ultrastructure; KVLQT1; human ether-a-go-go-related gene; long QT syndrome

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