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Differential calcineurin/NFATc3 activity contributes to the Ito transmural gradient in the mouse heart.
Circ Res. 2006 May 26; 98(10):1306-13.CircR

Abstract

Kv4 channels are differentially expressed across the mouse left ventricular free wall. Accordingly, the transient outward K+ current (Ito), which is produced by Kv4 channels, is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells. However, the mechanisms underlying heterogeneous Kv4 expression in the heart are unclear. Here, we tested the hypothesis that differential [Ca2+]i and calcineurin/NFATc3 signaling in EPI and ENDO cells contributes to the gradient of Ito function in the mouse left ventricle. In support of this hypothesis, we found that [Ca2+]i, calcineurin, and NFAT activity were greater in ENDO than in EPI myocytes. However, the amplitude of Ito was the same in ENDO and EPI cells when [Ca2+]i, calcineurin, and NFAT activity were equalized. Consistent with this, we observed complete loss of Ito and Kv4 heterogeneity in NFATc3-null mice. Interestingly, Kv4.3, Kv4.2, and KChIP2 genes had different apparent thresholds for NFATc3-dependent suppression and were ordered as Kv4.3 approximately KChIP2>Kv4.2. Based on these data, we conclude that calcineurin and NFATc3 constitute a Ca(2+)-driven signaling module that contributes to the nonuniform distribution of Kv4 expression, and hence Ito function, in the mouse left ventricle.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Washington, Seattle, WA 98118, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16614306

Citation

Rossow, Charles F., et al. "Differential calcineurin/NFATc3 Activity Contributes to the Ito Transmural Gradient in the Mouse Heart." Circulation Research, vol. 98, no. 10, 2006, pp. 1306-13.
Rossow CF, Dilly KW, Santana LF. Differential calcineurin/NFATc3 activity contributes to the Ito transmural gradient in the mouse heart. Circ Res. 2006;98(10):1306-13.
Rossow, C. F., Dilly, K. W., & Santana, L. F. (2006). Differential calcineurin/NFATc3 activity contributes to the Ito transmural gradient in the mouse heart. Circulation Research, 98(10), 1306-13.
Rossow CF, Dilly KW, Santana LF. Differential calcineurin/NFATc3 Activity Contributes to the Ito Transmural Gradient in the Mouse Heart. Circ Res. 2006 May 26;98(10):1306-13. PubMed PMID: 16614306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential calcineurin/NFATc3 activity contributes to the Ito transmural gradient in the mouse heart. AU - Rossow,Charles F, AU - Dilly,Keith W, AU - Santana,Luis F, Y1 - 2006/04/13/ PY - 2006/4/15/pubmed PY - 2006/6/13/medline PY - 2006/4/15/entrez SP - 1306 EP - 13 JF - Circulation research JO - Circ Res VL - 98 IS - 10 N2 - Kv4 channels are differentially expressed across the mouse left ventricular free wall. Accordingly, the transient outward K+ current (Ito), which is produced by Kv4 channels, is greater in left ventricular epicardial (EPI) than in endocardial (ENDO) cells. However, the mechanisms underlying heterogeneous Kv4 expression in the heart are unclear. Here, we tested the hypothesis that differential [Ca2+]i and calcineurin/NFATc3 signaling in EPI and ENDO cells contributes to the gradient of Ito function in the mouse left ventricle. In support of this hypothesis, we found that [Ca2+]i, calcineurin, and NFAT activity were greater in ENDO than in EPI myocytes. However, the amplitude of Ito was the same in ENDO and EPI cells when [Ca2+]i, calcineurin, and NFAT activity were equalized. Consistent with this, we observed complete loss of Ito and Kv4 heterogeneity in NFATc3-null mice. Interestingly, Kv4.3, Kv4.2, and KChIP2 genes had different apparent thresholds for NFATc3-dependent suppression and were ordered as Kv4.3 approximately KChIP2>Kv4.2. Based on these data, we conclude that calcineurin and NFATc3 constitute a Ca(2+)-driven signaling module that contributes to the nonuniform distribution of Kv4 expression, and hence Ito function, in the mouse left ventricle. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/16614306/Differential_calcineurin/NFATc3_activity_contributes_to_the_Ito_transmural_gradient_in_the_mouse_heart_ DB - PRIME DP - Unbound Medicine ER -