Abstract
To understand molecular mechanisms that regulate formation and maintenance of cardiac IKr (rapidly activating component of the delayed rectifier K+ current), we have investigated the spatiotemporal expression pattern of two rat potassium voltage-gated channels, namely subfamily H (eag-related), member2 (KCNH2) (alias name: rERG) and Isk-related family, member2 (KCNE2) (alias name: rMiRP1) during late embryonic development by means of the in situ hybridization technique. KCNE2 is transcribed predominantly in atrial und ventricular myocardium at stages E14.5-E18.5dpc and only a minor signal emerged in the tongue at E16.5dpc. In contrast, KCNH2 transcripts appeared in a less confined pattern with intense signals in atrial and ventricular myocardium, somites, spinal cord, bowel system, central nervous system and thymus at stages E14.5-E18.5dpc. Non-cardiac expression even exceeds the intensity of the cardiac signal, indicating that KCNH2 contributes to K+ currents in non-cardiac tissue as well. Transcription of the rat b-subunit KCNE2 is present in all regions of the fetal myocardium and co-distributes perfectly with transcription of the pore forming a-subunit KCNH2. It seems likely that KCNH2 and KCNE2 are linked to form cardiac IKr channels, associated to cardiogenesis and cardiomyocyte excitability.
Highlights
Repolarization in phase III of the cardiac action potential is dependent on the rapidly activating component of the delayed rectifier K+ current (IKr)
Native IKr channels and potassium voltage-gated channel (KCNH2) channels differ in their functional behavior indicating an assembling with additional potassium channel subunits to establish the cardiac IKr current. (Sanguinetti et al, 1995; Sanguinetti et al, 1996)
Mutations in KCNH2 and potassium voltage-gated channel (KCNE2) are associated with the long QT syndrome (LQTS), a cardiac disorder, which causes a prolongation of the cardiac action potential leading to polymorphic ventricular arrhythmias and sudden cardiac death (Sanguinetti et al, 1996; Abbott et al.,1999)
Summary
Repolarization in phase III of the cardiac action potential is dependent on the rapidly activating component of the delayed rectifier K+ current (IKr). The KCNE2 subunit gene, was reported to be expressed in a more restricted fashion with high level of mRNA in heart and striated muscle of adult rats (Abbott et al.,1999), which might imply that formation and myocardial specificity of IKr is due to the small potassium channel subunit KCNE2. In this regard, Tinel et al (2000) reported that KCNE2 is highly expressed in adult human brain, heart, striated muscle, pancreas, placenta, kidney, colon and thymus and is present on a lower level in liver, ovary, testis, prostate, small intestine and leucocyte. We investigated the expression of the IKr forming components KCNH2 and KCNE2 during late embryonic development of the rat and found that both IKr forming components were expressed in the atrial and ventricular chambers of the fetal rat heart
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