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Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2.
Am J Physiol Heart Circ Physiol. 2014 Apr 01; 306(7):H1054-65.AJ

Abstract

In the present study, we examined if and how cardiac ion channels are modified by type 2 diabetes mellitus (T2DM). Subendocardial (Endo) myocytes and subepicardial (Epi) myocytes were isolated from left ventricles of Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) rats, a rat model of T2DM, and Otsuka-Long-Evans-Tokushima (LETO) rats (nondiabetic control rats). Endo and Epi myocytes were used for whole cell patch-clamp recordings and for protein and mRNA analyses. Action potential durations in Endo and Epi myocytes were longer in OLETF rats than in LETO rats, and the difference was larger in Endo myocytes. Steady-state transient outward K+ current (Ito) density was reduced in Endo but not Epi myocytes of OLETF rats compared with LETO rats, although the contribution of the fast component of Ito recovery from inactivation was smaller in both Endo and Epi myocytes of OLETF rats than in LETO rats. Kv4.2 protein was reduced only in Endo myocytes in OLETF rats, although voltage-gated K+ channel-interacting protein 2 (KChIP2) protein levels in both Endo and Epi myocytes were lower in OLETF rats than in LETO rats. Corresponding regional differences in mRNA levels of KChIP2 and Kv4.2 were observed between OLETF and LETO rats. mRNA levels of Iroquois homeobox 5 in Endo myocytes were 53% higher in OLETF rats than in LETO rats. Densities of inward rectifier K+ current and L-type Ca2+ current and mRNA levels of Kv4.3 and Kv1.4 were similar in OLETF and LETO rats. In conclusion, T2DM induces Endo-predominant prolongation of the action potential duration via a reduction of the fast component of Ito recovery from inactivation and reduced steady-state Ito, in which downregulation of Kv4.2 and KChIP2 may be involved. Increased Iroquois homeobox 5 expression may underlie Kv4.2 downregulation in T2DM.

Authors+Show Affiliations

Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo, Japan;No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

24486512

Citation

Sato, Tatsuya, et al. "Type 2 Diabetes Induces Subendocardium-predominant Reduction in Transient Outward K+ Current With Downregulation of Kv4.2 and KChIP2." American Journal of Physiology. Heart and Circulatory Physiology, vol. 306, no. 7, 2014, pp. H1054-65.
Sato T, Kobayashi T, Kuno A, et al. Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2. Am J Physiol Heart Circ Physiol. 2014;306(7):H1054-65.
Sato, T., Kobayashi, T., Kuno, A., Miki, T., Tanno, M., Kouzu, H., Itoh, T., Ishikawa, S., Kojima, T., Miura, T., & Tohse, N. (2014). Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2. American Journal of Physiology. Heart and Circulatory Physiology, 306(7), H1054-65. https://doi.org/10.1152/ajpheart.00414.2013
Sato T, et al. Type 2 Diabetes Induces Subendocardium-predominant Reduction in Transient Outward K+ Current With Downregulation of Kv4.2 and KChIP2. Am J Physiol Heart Circ Physiol. 2014 Apr 1;306(7):H1054-65. PubMed PMID: 24486512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2. AU - Sato,Tatsuya, AU - Kobayashi,Takeshi, AU - Kuno,Atsushi, AU - Miki,Takayuki, AU - Tanno,Masaya, AU - Kouzu,Hidemichi, AU - Itoh,Takahito, AU - Ishikawa,Satoko, AU - Kojima,Takashi, AU - Miura,Tetsuji, AU - Tohse,Noritsugu, Y1 - 2014/01/31/ PY - 2014/2/4/entrez PY - 2014/2/4/pubmed PY - 2014/5/27/medline KW - Iroquois homeobox 5 KW - Kv4.2 KW - cardiac ion channel remodeling KW - type 2 diabetes KW - voltage-gated K+ channel-interacting protein 2 SP - H1054 EP - 65 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 306 IS - 7 N2 - In the present study, we examined if and how cardiac ion channels are modified by type 2 diabetes mellitus (T2DM). Subendocardial (Endo) myocytes and subepicardial (Epi) myocytes were isolated from left ventricles of Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) rats, a rat model of T2DM, and Otsuka-Long-Evans-Tokushima (LETO) rats (nondiabetic control rats). Endo and Epi myocytes were used for whole cell patch-clamp recordings and for protein and mRNA analyses. Action potential durations in Endo and Epi myocytes were longer in OLETF rats than in LETO rats, and the difference was larger in Endo myocytes. Steady-state transient outward K+ current (Ito) density was reduced in Endo but not Epi myocytes of OLETF rats compared with LETO rats, although the contribution of the fast component of Ito recovery from inactivation was smaller in both Endo and Epi myocytes of OLETF rats than in LETO rats. Kv4.2 protein was reduced only in Endo myocytes in OLETF rats, although voltage-gated K+ channel-interacting protein 2 (KChIP2) protein levels in both Endo and Epi myocytes were lower in OLETF rats than in LETO rats. Corresponding regional differences in mRNA levels of KChIP2 and Kv4.2 were observed between OLETF and LETO rats. mRNA levels of Iroquois homeobox 5 in Endo myocytes were 53% higher in OLETF rats than in LETO rats. Densities of inward rectifier K+ current and L-type Ca2+ current and mRNA levels of Kv4.3 and Kv1.4 were similar in OLETF and LETO rats. In conclusion, T2DM induces Endo-predominant prolongation of the action potential duration via a reduction of the fast component of Ito recovery from inactivation and reduced steady-state Ito, in which downregulation of Kv4.2 and KChIP2 may be involved. Increased Iroquois homeobox 5 expression may underlie Kv4.2 downregulation in T2DM. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/24486512/Type_2_diabetes_induces_subendocardium_predominant_reduction_in_transient_outward_K+_current_with_downregulation_of_Kv4_2_and_KChIP2_ DB - PRIME DP - Unbound Medicine ER -