Journal: Nature Communications

Article Title: Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy

doi: 10.1038/ncomms11067

Figure Lengend Snippet: ( a ) Schematic representation of mutually exclusive exons 6A and 6B of Scn5a and of antisense sequences driven by optimized U7-snRNAs (U7-AS Scn5a ) to force fetal exon 6A inclusion in adult wild-type mouse heart. ( b , upper) RT–PCR analysis of the alternative splicing of endogenous Scn5a mRNA from heart samples of mice injected with AAV2/9 expressing U7-AS Scn5a compared with control injected mice. Molecular size marker is indicated in bp. (lower) Percentage of Scn5a mRNA including exon 6A. ( c ) Real-time RT-qPCR quantification of the expression of Scn5a, Scn1b and GJja1 (connexin 43) mRNAs in heart samples of mice expressing U7-AS Scn5a ( n =6) compared with control injected mice ( n =6). ( d ) Representative ECG traces show prolongation of the PR interval in U7-AS Scn5a -injected mice compared with control mice. ( e ) ECG measures of PR interval, QRS and QT intervals in 4-month-old mice injected with AAV2/9 expressing U7-AS Scn5a ( n =25) compared with age-matched control mice ( n =17). ( f ) Representative ECG traces reveal atrial fibrillation in U7-AS Scn5a -injected mice compared with control mice. ( g ) Variation of the RR interval indicates evidences of heart arrhythmias in U7-AS Scn5a -injected mice ( n =25) compared with control mice ( n =17). ( h ) Representative image of six analysed heart samples showing mild fibrosis revealed by Red Sirius histology staining in AAV-U7-AS Scn5a -injected mice. Scale bar, 100 μm. ( i ) Real-time RT-qPCR quantification of the expression of Cola1a, Col3a1 and Tgfb mRNAs in heart of control ( n =6) or AAV-U7-AS Scn5a -injected mice ( n =6). Bars indicate s.e.m. Student test, * indicates P <0.5, ** indicates P <0.01, *** indicates P <0.001. bp, base pair.

Article Snippet: Heart rate, PR and QRS duration were measured from recording traces using ECG auto V.1.5.7 software (Emka Technologies).

Techniques: Reverse Transcription Polymerase Chain Reaction, Alternative Splicing, Injection, Expressing, Control, Marker, Quantitative RT-PCR, Staining

Journal: Nature Communications

Article Title: Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy

doi: 10.1038/ncomms11067

Figure Lengend Snippet: ( a ) Simulations of ECG (upper) and action potential (AP) alterations (middle and lower) caused by the switch from adult SCN5A exon 6B towards fetal exon 6A, using a modified human ventricular ORd model. ( b ) Simulations of the atrio-ventricular changes caused by inclusion of SCN5A fetal exon 6A instead of adult exon 6B, employing an atrio-ventricular nodal model. APs of atrial and AV node cells were simulated and atrium-His interval was measured as the difference in the latency of APs between atrial and nodal-His cells. ( c ) Model of splicing alteration of the cardiac sodium channel, SCN5A , in DM. MBNL proteins regulate the switch from SCN5A exon 6A in fetal heart to exon 6B in adult. In DM, titration of MBNL proteins by mutant RNA containing expanded CUG repeats leads to expression of a fetal splicing form of SCN5A , inappropriate to adult heart physiology, ultimately resulting in cardiac-conduction delay and heart arrhythmias, which are two keys features of DM.

Article Snippet: Heart rate, PR and QRS duration were measured from recording traces using ECG auto V.1.5.7 software (Emka Technologies).

Techniques: Modification, Titration, Mutagenesis, Expressing

Journal: Psychopharmacology

Article Title: Myocardial infarction sensitizes medial prefrontal cortex to inhibitory effect of locus coeruleus stimulation in rats

doi: 10.1007/s00213-016-4305-y

Figure Lengend Snippet: Example of ECG waveforms collected during LC stimulation in a rat subjected to CAL (a). Three sequential ECG waveforms are shown in each row. Sequential wave forms are shown before start of stimulation (Pre-stim), during stimulation and after stimulation (Post-stim). Note that arrhythmias unique from the prestimulus baseline rhythms develop midway through stimulation and did not revert immediately upon cessation of LC stimulation. bVertical plots indicating percent bigeminy, preventricular contraction (PVC), and ventricular tachycardic (VT) rhythms detected during real or mock LC stimulation in rats subjected to CAL and sham ligation. Symbols represent percent of total waveforms (beats) detected during real or mock stimulation that were of the specified waveform subtype and distinct from any waveform detected during the prestimulus time period for each individual animal. Horizontal bar indicates group mean, and vertical bar is SEM; **P < 0.01

Article Snippet: The ECG pattern recognition software ECG-Auto (EMKA Technologies, Falls Church, VA) was used to detect arrhythmias.

Techniques: Ligation