Adult KCNE1-knockout mice exhibit a mild cardiac cellular phenotype.
The KCNE1 gene encodes a channel regulator IsK which in association with the KvLQT1 K+ channel protein determines the slow component of the cardiac delayed rectifier current. We have investigated the cellular electrophysiological characteristics of adult KCNE1-knockout mouse hearts by means of the standard microelectrode technique. Action potential parameters from the ventricular endocardium of KCNE1 -/- mice were indistinguishable from those of KCNE1 +/+ animals. In particular, KCNE1 -/- hearts did not exhibit prolonged repolarization. E-4031, a specific blocker of erg K+ channels consistently prolonged repolarization in KCNE1 +/+ but not in KCNE1 -/- hearts. By contrast, the chromanol compound 293B, a specific blocker of KvLQT1 K+ channel produced comparable effects on repolarization in KCNE1 -/- and KCNE1 +/+ mice. We conclude that invalidation of the mouse KCNE1 gene by homologous recombination leads to a mild cardiac phenotype at the cellular level.
Charpentier
F
F
Laboratoire de Physiopathologie & Pharmacologie Cellulaires & Moléculaires, INSERM, Nantes, CJF96-01, France.
Merot
J
J
Riochet
D
D
Le Marec
H
H
Escande
D
D
D000200:Action Potentials; D000818:Animals; D002839:Chromans / Q000494:pharmacology; D004553:Electric Conductivity; D004594:Electrophysiology / Q000379:methods; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006720:Homozygote; D066298:In Vitro Techniques; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010507:Periodicity; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D002839:Chromans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D010880:Piperidines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011725:Pyridines; D013449:Sulfonamides; C059983:potassium channel protein I(sk); C063968:E 4031; C103474:6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethylchromane