ADULT KCNE1-KNOCKOUT MICE EXHIBIT A MILD CARDIAC CELLULAR PHENOTYPE

The KCNE1 gene encodes a channel regulator IsK which in association wi th the KvLQT1 K+ channel protein determines the slow component of the cardiac delayed rectifier current. We have investigated the cellular e lectrophysiological characteristics of adult KCNE1-knockout mouse hear ts by means of the standard microelectrode technique. Action potential parameters from the ventricular endocardium of KCNE1 -/- mice were in distinguishable from those of KCNE1 +/+ animals. In particular, KCNE1 -/- hearts did not exhibit prolonged repolarization. E-4031, a specifi c blocker of erg Kf channels consistently prolonged repolarization in KCNE1 +/+ but not in KCNE1 -/- hearts. By contrast, the chromanol comp ound 293B, a specific blocker of KvLQT1 K+ channel produced comparable effects on repolarization in KCNE1 -/- and KCNE1 +/+ mice. We conclud e that invalidation of the mouse KCNE1 gene by homologous recombinatio n leads to a mild cardiac phenotype at the cellular level. (C) 1998 Ac ademic Press.