Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy

Suzuki, Takahiro; Takimoto, Koichi

doi:10.1152/ajpendo.00250.2004

Cited by 20 publications

(23 citation statements)

References 32 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…28 To detect KChIP2 proteins, we used polyclonal and monoclonal anti-KChIP2 antibodies. 26,31 These antibodies specifically reacted with all three KChIP2 splicing variants ( Figure 1C with monoclonal antibody and data with polyclonal antibody not shown). Rat brains contained immunoreactive KChIP2 proteins with distinct sizes: a doublet at Ϸ30 KDa and a band at Ϸ25 KDa ( Figure 1C).…”

mentioning

confidence: 72%

“…Kv4 and KChIP2 subunit mRNA levels were determined by RNase protection and real-time PCR, respectively, according to the previously described methods. 26,27 For the latter analysis, we used primers corresponding to the C-terminal portion of KChIP2 cDNA that was commonly present in all splicing variants. 26 We also used standard RT-PCR for detection and quantitation of KChIP2 splicing variants.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mitogen-Activated Protein Kinases Control Cardiac KChIP2 Gene Expression

Jia

Takimoto

2006

Circulation Research

Self Cite

View full text Add to dashboard Cite

Abstract-Hypertrophied myocardium is associated with reductions in the transient outward K ϩ current (Ito) and expression of pore-forming Kv4.2/4.3 and auxiliary KChIP2 subunits. Here we show that KChIP2 mRNA and protein levels are dramatically decreased to 10% to 30% of control levels in the left ventricle of aorta-constricted rats in vivo and phenylephrine (PE)-treated myocytes in vitro. PE also markedly decreases Ito density. Inhibition of protein kinase Cs (PKCs) does not affect the PE-induced reduction in KChIP2 mRNA level, whereas activation of PKC with phorbol ester (phorbol myristate [PMA]) causes a marked reduction in KChIP2 mRNA level. Pharmacological inhibition of MEKs or overexpression of a dominant-negative MEK1 increases the basal KChIP2 mRNA expression and blocks the PMA-induced decrease in auxiliary subunit mRNA level. In addition, a constitutively active MEK1 decreases the basal KChIP2 mRNA level, and PMA causes no further reduction in auxiliary subunit mRNA level in active MEK1-expressing cells. Furthermore, pharmacological inhibition of JNKs or overexpression of a dominant-negative JNK1 prevents the PE-induced, but not PMA-induced, reduction in KChIP2 mRNA expression. These results suggest that downregulation of KChIP2 expression significantly contributes to the hypertrophy-associated reduction in Ito density. They also indicate that the expression of KChIP2 mRNA is controlled by the 2 branches of mitogen-activated protein kinase pathways: JNKs play a predominant role in mediating the PE-induced reduction, whereas the MEK-ERK pathway influences the basal expression and mediates the PKC-mediated downregulation. ardiac hypertrophy develops as a biological compensatory change in response to increased workload. However, sustained hypertrophy is a major risk factor for cardiac morbidity and mortality. 1,2 One of the commonly observed changes in hypertrophied myocardium is a reduction in transient outward K ϩ current (Ito). 3 Although it remains uncertain whether and how this reduction contributes to the increased cardiac dysfunction and sudden death seen with patients with hypertrophy, recent studies suggest that a marked reduction in Ito can be detrimental. For example, Ito is differentially expressed in distinct parts of the heart. 4 -11 Elimination of this differential expression may result in electrical instability by diminishing regional differences in action potential. 12 Likewise, decreased Ito can facilitate the development of cardiac hypertrophy by prolonging action potential duration and a window for Ca 2ϩ entry. 13,14 Thus, an uncontrolled decline in Ito channel expression may directly or indirectly participate in the induction of hypertrophy-associated pathological changes of the heart. Although Kv1.4-containing Kv1-family channels contribute to cardiac Ito, a large portion of the current is attributable to channels in the Kv4 family. 15 Materials and Methods Animals and Neonatal Myocyte CultureAbdominal aortic constriction or sham operation was performed on male Sprague-Dawley rats (1...

show abstract

mentioning

confidence: 72%

mentioning

confidence: 99%

Mitogen-Activated Protein Kinases Control Cardiac KChIP2 Gene Expression

Jia

Takimoto

2006

Circulation Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Electrophysiological studies have described rapidly inactivating K + current in rat pregnant myometrium generated by the Kv4 family of K + channels [56]. Of this channel subfamily, Kv4.2 and their accessory subunits increased before parturition, whereas Kv4.1 and Kv4.3 expression declined during gestation suggesting that soluble factors, possibly hormones, regulate Kv4 channels in pregnancy [56]. This was further supported by research showing that in ovariectomized rats, estrogen down-regulated membrane localization, protein and current expression of Kv4.3 channels [57].…”

Section: Bkca Channelsmentioning

confidence: 99%

“…One of these subunits is the Kv channel interacting proteins (KChIPs), which are calcium-binding proteins [61]. Two isoforms, KChIP2 and 4 have been found in the myometrium [56]. In rats, KChIP2 is upregulated in late gestation, and enhances Kv4 channels cell membrane density by trafficking channels from the endoplasmic reticulum to the cell membrane.…”

Section: Bkca Channelsmentioning

confidence: 99%

Potassium channels and uterine function

Brainard

Korovkina

England

2007

Seminars in Cell & Developmental Biology

102

108

View full text Add to dashboard Cite

Ion channels are effector proteins that mediate uterine excitability throughout gestation. This review will focus primarily on the role of potassium channels in regulating myometrial tone in pregnancy and labor contractions. During gestation, potassium channels maintain the uterus in a state of quiescence by contributing to the resting membrane potential and counteracting contractile stimuli. This review summarizes the current knowledge about the significance of the potassium channels in maintaining a normal gestational period and initiating labor contractions at term.

show abstract

“…Some ion channels have been studied in the myometrium during pregnancy (Suzuki & Takimoto 2005, Xu et al 2011. Aquaporins 3, 4, 5 and 8 are involved in fluid homoeostasis in pregnant and peripartum cervices, thus facilitating water transport across the cervical epithelium (Anderson et al 2006).…”

Section: Introductionmentioning

confidence: 99%

KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone

et al. 2013

View full text Add to dashboard Cite

Potassium voltage-gated channel, subfamily H (eag-related), member 1 (KCNH1) potassium channels are potential tumour markers and cancer therapeutic targets and are up-regulated by oestrogens and human papilloma virus (HPV) oncogenes. However, the role of KCNH1 in normal tissues is poorly understood, and its expression in pregnancy is unknown. We wondered whether KCNH1 channels are expressed in cervical cells from pregnant patients and whether progesterone (P 4 ) regulates KCNH1. The association with HPV was also investigated. KCNH1 protein expression was studied by immunocytochemistry in liquid-based cervical cytologies; 93 samples were obtained from pregnant patients at different trimesters, and 15 samples were obtained from non-pregnant women (controls). The presence of HPV was studied by PCR with direct sequencing and nested multiplex PCR. HeLa cervical cancer cells were transfected with human progesterone receptor-B (PR-B) and treated with P 4 . KCNH1 mRNA expression in these cultures was studied by real-time PCR. KCNH1 protein was detected in 100% of the pregnancy samples and in 26% of the controls. We found 18 pregnant patients infected with HPV and detected 14 types of HPV. There was no association between the percentage of cells expressing KCNH1 and either the presence or type of HPV. P 4 induced KCNH1 mRNA and protein expression in cells transfected with human PR-B. No regulation of KCNH1 by P 4 was observed in non-transfected cells. We show for the first time the expression of an ion channel during human pregnancy at different trimesters and KCNH1 regulation by P 4 in human cells. These data raise a new research field for KCNH1 channels in human tissues.

show abstract

Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy

Cited by 20 publications

References 32 publications

Mitogen-Activated Protein Kinases Control Cardiac KChIP2 Gene Expression

Mitogen-Activated Protein Kinases Control Cardiac KChIP2 Gene Expression

Potassium channels and uterine function

KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone

Contact Info

Product

Resources

About