Kcnq1 contributes to an adrenergic-sensitive steady-state K+ current in mouse heart.
It has been suggested that Kcne1 subunits are required for adrenergic regulation of Kcnq1 potassium channels. However, in adult mouse hearts, which do not express Kcne1, loss of Kcnq1 causes a Long QT phenotype during adrenergic challenge, raising the possibility that native Kcnq1 currents exist and are adrenergically regulated even in absence of Kcne1. Here, we used immunoblotting and immunohistochemical staining to show that Kcnq1 protein is present in adult mouse hearts. Voltage-clamp experiments demonstrated that Kcnq1 contributes to a steady-state outward current (I(SS)) in wild-type (Kcnq1(+/+)) ventricular myocytes during isoproterenol stimulation, resulting in a significant 7.1% increase in I(SS) density (0.43+/-0.16 pA/pF, p <0.05, n =15), an effect that was absent in Kcnq1-deficient (Kcnq1(-/-)) myocytes (-0.14+/-0.13 pA/pF, n =17). These results demonstrate for the first time that Kcnq1 protein is expressed in adult mouse hearts where it contributes to a beta-adrenergic-induced component of I(SS) that does not require co-assembly with Kcne1.
Knollmann
Bjorn C
BC
Department of Pharmacology, Georgetown University Medical Center, Washington, DC, USA.
Sirenko
Syevda
S
Rong
Qi
Q
Katchman
Alexander N
AN
Casimiro
Mathew
M
Pfeifer
Karl
K
Ebert
Steven N
SN
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000008:administration & dosage*; D051657:KCNQ1 Potassium Channel / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D014018:Tissue Distribution
D000318:Adrenergic beta-Agonists; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D007545:Isoproterenol; D011188:Potassium