Channelpedia

PubMed 16293790


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KChip2a , Kv1.4 , Kv1.5 , Kv2.1 , Kv3.1 , Kv4.2 , Kv4.3 , Slo1



Title: Targeted deletion of Kv4.2 eliminates I(to,f) and results in electrical and molecular remodeling, with no evidence of ventricular hypertrophy or myocardial dysfunction.

Authors: Weinong Guo, W Edward Jung, Céline Marionneau, Franck Aimond, Haodong Xu, Kathryn A Yamada, Thomas L Schwarz, Sophie Demolombe, Jeanne M Nerbonne

Journal, date & volume: Circ. Res., 2005 Dec 9 , 97, 1342-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16293790


Abstract
Previous studies have demonstrated a role for voltage-gated K+ (Kv) channel alpha subunits of the Kv4 subfamily in the generation of rapidly inactivating/recovering cardiac transient outward K+ current, I(to,f), channels. Biochemical studies suggest that mouse ventricular I(to,f) channels reflect the heteromeric assembly of Kv4.2 and Kv4.3 with the accessory subunits, KChIP2 and Kvbeta1, and that Kv4.2 is the primary determinant of regional differences in (mouse ventricular) I(to,f) densities. Interestingly, the phenotypic consequences of manipulating I(to,f) expression in different mouse models are distinct. In the experiments here, the effects of the targeted deletion of Kv4.2 (Kv4.2(-/-)) were examined. Unexpectedly, voltage-clamp recordings from Kv4.2(-/-) ventricular myocytes revealed that I(to,f) is eliminated. In addition, the slow transient outward K+ current, I(to,s), and the Kv1.4 protein (which encodes I(to,s)) are upregulated in Kv4.2(-/-) ventricles. Although Kv4.3 mRNA/protein expression is not measurably affected, KChIP2 expression is markedly reduced in Kv4.2(-/-) ventricles. Similar to Kv4.3, expression of Kvbeta1, as well as Kv1.5 and Kv2.1, is similar in wild-type and Kv4.2(-/-) ventricles. In addition, and in marked contrast to previous findings in mice expressing a truncated Kv4.2 transgene, the elimination I(to,f) in Kv4.2(-/-) mice does not result in ventricular hypertrophy. Taken together, these findings demonstrate not only an essential role for Kv4.2 in the generation of mouse ventricular I(to,f) channels but also that the loss of I(to,f) per se does not have overt pathophysiological consequences.