TY - JOUR
T1 - Kv4.3 is not required for the generation of functional Ito,f channels in adult mouse ventricles
AU - Niwa, Noriko
AU - Wang, Wei
AU - Sha, Qun
AU - Marionneau, Céline
AU - Nerbonne, Jeanne M.
N1 - Funding Information:
The authors wish to thank Mr. Jefferson Gomes and Ms. Amy Coleman for their assistance with myocyte isolations, and Mr. Rick Wilson for screening and maintaining the Kv4.3−/− mouse colony. The authors also thank the National Institutes of Health (HL-034161 and HL-066388 to JMN) and the Heartland Affiliate of the American Heart Association (Postdoctoral Fellowship to CM) for the financial support provided.
PY - 2008/1
Y1 - 2008/1
N2 - Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current (Ito,f) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular Ito,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3-/-) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3-/- hearts. Voltage-clamp recordings revealed that functional Ito,f channels are expressed in Kv4.3-/- ventricular myocytes, and that mean Ito,f densities are similar to those recorded from wild-type cells. In addition, Ito,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3-/- and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3-/- ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular Ito,f channels.
AB - Accumulated evidence suggests that the heteromeric assembly of Kv4.2 and Kv4.3 α-subunits underlies the fast transient Kv current (Ito,f) in rodent ventricles. Recent studies, however, demonstrated that the targeted deletion of Kv4.2 results in the complete elimination of Ito,f in adult mouse ventricles, revealing an essential role for the Kv4.2 α-subunit in the generation of mouse ventricular Ito,f channels. The present study was undertaken to investigate directly the functional role of Kv4.3 by examining the effects of the targeted disruption of the KCND3 (Kv4.3) locus. Mice lacking Kv4.3 (Kv4.3-/-) appear indistinguishable from wild-type control animals, and no structural or functional abnormalities were evident in Kv4.3-/- hearts. Voltage-clamp recordings revealed that functional Ito,f channels are expressed in Kv4.3-/- ventricular myocytes, and that mean Ito,f densities are similar to those recorded from wild-type cells. In addition, Ito,f properties (inactivation rates, voltage dependences of inactivation and rates of recovery from inactivation) in Kv4.3-/- and wild-type mouse ventricular myocytes were indistinguishable. Quantitative RT-PCR and Western blot analyses did not reveal any measurable changes in the expression of Kv4.2 or the Kv channel interacting protein (KChIP2) in Kv4.3-/- ventricles. Taken together, the results presented here suggest that, in contrast with Kv4.2, Kv4.3 is not required for the generation of functional mouse ventricular Ito,f channels.
KW - Heteromeric Kv channels
KW - KCND3
KW - Kv channels
KW - Kv α-subunits
UR - http://www.scopus.com/inward/record.url?scp=37549055114&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2007.10.007
DO - 10.1016/j.yjmcc.2007.10.007
M3 - Article
C2 - 18045613
AN - SCOPUS:37549055114
SN - 0022-2828
VL - 44
SP - 95
EP - 104
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 1
ER -