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SUBUNIT
1 Molecular Biology and Pharmacology, Washington University, St.Louis, MO, USA
2 Internal Medicine, Washington University, St.Louis, MO, USA
* To whom correspondence should be addressed. E-mail: jnerbonne{at}msnotes.wustl.edu.
Although previous studies have revealed a role for Kv1.5 in the generation of mouse ventricular IK,slow1, the phenotypic consequences of manipulating IK,slow1 expression in vivo in different (mouse) models are distinct. In the experiments here, point mutations were introduced in the pore region of Kv1.5 to change the tryptophan (W) at position 461 to phenylalanine (F) to produce a non-conducting subunit, Kv1.5W461F, that is shown to function as a Kv1 subfamily-specific dominant negative (Kv1.5DN). Using the 
-myosin heavy chain promoter to direct cardiac-specific expression, three lines of Kv1.5DN-expressing (C57BL6) transgenic mice were generated and characterized. Electrophysiological recordings from Kv1.5-DN-expressing left ventricular myocytes revealed that the µM 4-aminopyridine (4-AP) sensitive IK,slow1 is selectively eliminated. The attenuation of IK,slow1 is accompanied by increased ventricular action potential durations and marked QT prolongation. In contrast to previous findings in mice expressing a truncated (dominant negative) Kv1.1 transgene, however, no electrical remodeling is evident in Kv1.5DN-expressing ventricular myocytes, and the (Kv1.5DN-induced) elimination of IK,slow1 does not result in spontaneous ventricular arrhythmias.
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