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Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats.
Cardiovasc Res. 2007 Apr 01; 74(1):85-95.CR

Abstract

OBJECTIVE

A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology.

METHODS

In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits.

RESULTS

I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high.

CONCLUSION

These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR.

Authors+Show Affiliations

Institut für Vegetative Physiologie und Pathophysiologie, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17289007

Citation

Goltz, Diane, et al. "Diminished Kv4.2/3 but Not KChIP2 Levels Reduce the Cardiac Transient Outward K+ Current in Spontaneously Hypertensive Rats." Cardiovascular Research, vol. 74, no. 1, 2007, pp. 85-95.
Goltz D, Schultz JH, Stucke C, et al. Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats. Cardiovasc Res. 2007;74(1):85-95.
Goltz, D., Schultz, J. H., Stucke, C., Wagner, M., Bassalaý, P., Schwoerer, A. P., Ehmke, H., & Volk, T. (2007). Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats. Cardiovascular Research, 74(1), 85-95.
Goltz D, et al. Diminished Kv4.2/3 but Not KChIP2 Levels Reduce the Cardiac Transient Outward K+ Current in Spontaneously Hypertensive Rats. Cardiovasc Res. 2007 Apr 1;74(1):85-95. PubMed PMID: 17289007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diminished Kv4.2/3 but not KChIP2 levels reduce the cardiac transient outward K+ current in spontaneously hypertensive rats. AU - Goltz,Diane, AU - Schultz,Jobst-Hendrik, AU - Stucke,Carolin, AU - Wagner,Michael, AU - Bassalaý,Peter, AU - Schwoerer,Alexander Peter, AU - Ehmke,Heimo, AU - Volk,Tilmann, Y1 - 2007/01/08/ PY - 2006/05/19/received PY - 2006/12/22/revised PY - 2007/01/02/accepted PY - 2007/2/10/pubmed PY - 2007/6/22/medline PY - 2007/2/10/entrez SP - 85 EP - 95 JF - Cardiovascular research JO - Cardiovasc Res VL - 74 IS - 1 N2 - OBJECTIVE: A reduction of the Ca(2+)-independent transient outward potassium current (I(to)) in epicardial but not in endocardial myocytes of the left ventricle has been observed in cardiac hypertrophy and is thought to contribute to the electrical vulnerability associated with this pathology. METHODS: In the present study we investigated the molecular mechanisms underlying regional alterations in I(to) in hypertrophied hearts of spontaneously hypertensive rats (SHR) using the whole-cell patch-clamp technique, quantitative RT-PCR and heterologous expression of underlying ion channel subunits. RESULTS: I(to) was significantly smaller in epicardial myocytes of SHR than in Wistar-Kyoto (WKY) controls (11.1+/-0.9 pA/pF, n=20 vs. 16.8+/-1.7 pA/pF, n=20, p<0.01), but not different in endocardial myocytes from both groups. Quantitative RT-PCR analysis of the genes encoding I(to) revealed significantly lower levels of Kv4.2 and Kv4.3 mRNA in the epicardial region of SHR rats compared to WKY rats. In contrast, mRNA expression levels of all three splice variants of the beta-subunit KChIP2 were significantly higher in both endo- and epicardial myocytes from SHR than from WKY rats. In parallel, inactivation of I(to), which is negatively modulated by KChIP2, was slowed down in SHR while recovery from inactivation remained unchanged. Heterologous co-expression of increasing amounts of KChIP2b together with a fixed amount of Kv4.2 in Xenopus laevis oocytes revealed a hyperbolic relation of recovery from inactivation and inactivation time constant, demonstrating that KChIP2 preferentially affects inactivation, if its expression level is high. CONCLUSION: These results suggest that downregulation of I(to) in the left ventricle of SHR is mediated by a reduced expression of Kv4.2 and Kv4.3 (but not of KChIP2), whereas the slower inactivation of I(to) can be explained by increased expression levels of KChIP2 in SHR. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/17289007/Diminished_Kv4_2/3_but_not_KChIP2_levels_reduce_the_cardiac_transient_outward_K+_current_in_spontaneously_hypertensive_rats_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/j.cardiores.2007.01.001 DB - PRIME DP - Unbound Medicine ER -