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The involvement of TRPC3 channels in sinoatrial arrhythmias.

Ju YK, Lee BH, Trajanovska S, Hao G, Allen DG, Lei M, Cannell MB - Front Physiol (2015)

Bottom Line: We will then present some of our recent research progress in this field.Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3(-/-) mice) compared to wild type controls.We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP3R.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, School of Medical Sciences, Bosch Institute, University of Sydney Sydney, NSW, Australia.

ABSTRACT
Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SAN). The association between AF and SAN dysfunction is probably related to the communication between the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker complex and/or pathological processes that affect both the SAN and atrial simultaneously. Recent evidence suggests that Ca(2+) entry through TRPC3 (Transient Receptor Potential Canonical-3) channels may underlie several pathophysiological conditions -including cardiac arrhythmias. However, it is still not known if atrial and sinoatrial node cells are also involved. In this article we will first briefly review TRPC3 and IP3R signaling that relate to store/receptor-operated Ca(2+) entry (SOCE/ROCE) mechanisms and cardiac arrhythmias. We will then present some of our recent research progress in this field. Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3(-/-) mice) compared to wild type controls. We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP3R. Activation of G-protein coupled receptors (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca(2+) homeostasis changes in sinoatrial complex being linked to TRPC3. The results provide new evidence that TRPC3 may play a role in sinoatrial and atrial arrhythmias that are caused by GPCRs activation.

No MeSH data available.


Related in: MedlinePlus

Atrial arrhythmias induced by Ang II and pacing. Reconstructed excitation maps of data from multi-electrode array recordings (images below) from a Langendorff-perfused isolated heart. (A) sinus rhythm and (B) pacing induced atrial tachycardia. Note in AT, the ectopic beat starts from a different site to sinus rhythms. (C) Representative ECG recordings from isolated heart from WT and TRPC3 −/− mice under control conditions. (D) Atrial tachycardia and atrial fibrillation induced by burst pacing in WT mice and atrial-ventricular conduction block recorded from a TRPC−/− mouse heart respectively. (E) On average, the arrhythmia index was significant reduced in TRPC3KO mice (n = 8) compared to WT mice (n = 11, P = 0.004).
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Figure 2: Atrial arrhythmias induced by Ang II and pacing. Reconstructed excitation maps of data from multi-electrode array recordings (images below) from a Langendorff-perfused isolated heart. (A) sinus rhythm and (B) pacing induced atrial tachycardia. Note in AT, the ectopic beat starts from a different site to sinus rhythms. (C) Representative ECG recordings from isolated heart from WT and TRPC3 −/− mice under control conditions. (D) Atrial tachycardia and atrial fibrillation induced by burst pacing in WT mice and atrial-ventricular conduction block recorded from a TRPC−/− mouse heart respectively. (E) On average, the arrhythmia index was significant reduced in TRPC3KO mice (n = 8) compared to WT mice (n = 11, P = 0.004).

Mentions: Ang II signaling pathways lead to a hypertrophy which seems to be related to TRPC3 expression (Onohara et al., 2006). To examine whether TRPC3 is involved in AF induced by Ang II, we induced AF in mice by pacing Langendorff-perfused hearts from WT and TRPC3−/− KO mice which had been treated with Ang II (See Methods) over of 10–14 days. Figure 2A shows the conduction of the AP across the SAN to the atria reconstructed from the timing of the recorded electrical signals (panel below) using a 36 mini electrode array placed on the right atrium. Atrial arrhythmic events are illustrated in Figure 2B, and were induced by using a pacing protocol that varied pacing voltage and frequency. To investigate the possible role of TRPC3 in these arrhythmias, we made ECG recordings from Langendorff-perfused hearts under control condition in WT and TRPC3−/− respectively, as shown in the selected recordings illustrated in Figure 2C. Electrical pacing induced AF, AT, and conduction block were recorded and analyzed in WT and TRPC3−/−, respectively (exemplar data shown in Figure 2D). We found that atrial arrhythmias induced by Ang II and pacing were significantly reduced in the TRPC3−/− mice compared to the controls (P = 0.004, n = 11) (Figure 2E).


The involvement of TRPC3 channels in sinoatrial arrhythmias.

Ju YK, Lee BH, Trajanovska S, Hao G, Allen DG, Lei M, Cannell MB - Front Physiol (2015)

Atrial arrhythmias induced by Ang II and pacing. Reconstructed excitation maps of data from multi-electrode array recordings (images below) from a Langendorff-perfused isolated heart. (A) sinus rhythm and (B) pacing induced atrial tachycardia. Note in AT, the ectopic beat starts from a different site to sinus rhythms. (C) Representative ECG recordings from isolated heart from WT and TRPC3 −/− mice under control conditions. (D) Atrial tachycardia and atrial fibrillation induced by burst pacing in WT mice and atrial-ventricular conduction block recorded from a TRPC−/− mouse heart respectively. (E) On average, the arrhythmia index was significant reduced in TRPC3KO mice (n = 8) compared to WT mice (n = 11, P = 0.004).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4373262&req=5

Figure 2: Atrial arrhythmias induced by Ang II and pacing. Reconstructed excitation maps of data from multi-electrode array recordings (images below) from a Langendorff-perfused isolated heart. (A) sinus rhythm and (B) pacing induced atrial tachycardia. Note in AT, the ectopic beat starts from a different site to sinus rhythms. (C) Representative ECG recordings from isolated heart from WT and TRPC3 −/− mice under control conditions. (D) Atrial tachycardia and atrial fibrillation induced by burst pacing in WT mice and atrial-ventricular conduction block recorded from a TRPC−/− mouse heart respectively. (E) On average, the arrhythmia index was significant reduced in TRPC3KO mice (n = 8) compared to WT mice (n = 11, P = 0.004).
Mentions: Ang II signaling pathways lead to a hypertrophy which seems to be related to TRPC3 expression (Onohara et al., 2006). To examine whether TRPC3 is involved in AF induced by Ang II, we induced AF in mice by pacing Langendorff-perfused hearts from WT and TRPC3−/− KO mice which had been treated with Ang II (See Methods) over of 10–14 days. Figure 2A shows the conduction of the AP across the SAN to the atria reconstructed from the timing of the recorded electrical signals (panel below) using a 36 mini electrode array placed on the right atrium. Atrial arrhythmic events are illustrated in Figure 2B, and were induced by using a pacing protocol that varied pacing voltage and frequency. To investigate the possible role of TRPC3 in these arrhythmias, we made ECG recordings from Langendorff-perfused hearts under control condition in WT and TRPC3−/− respectively, as shown in the selected recordings illustrated in Figure 2C. Electrical pacing induced AF, AT, and conduction block were recorded and analyzed in WT and TRPC3−/−, respectively (exemplar data shown in Figure 2D). We found that atrial arrhythmias induced by Ang II and pacing were significantly reduced in the TRPC3−/− mice compared to the controls (P = 0.004, n = 11) (Figure 2E).

Bottom Line: We will then present some of our recent research progress in this field.Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3(-/-) mice) compared to wild type controls.We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP3R.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, School of Medical Sciences, Bosch Institute, University of Sydney Sydney, NSW, Australia.

ABSTRACT
Atrial fibrillation (AF) is a significant contributor to cardiovascular morbidity and mortality. The currently available treatments are limited and AF continues to be a major clinical challenge. Clinical studies have shown that AF is frequently associated with dysfunction in the sino-atrial node (SAN). The association between AF and SAN dysfunction is probably related to the communication between the SAN and the surrounding atrial cells that form the SAN-atrial pacemaker complex and/or pathological processes that affect both the SAN and atrial simultaneously. Recent evidence suggests that Ca(2+) entry through TRPC3 (Transient Receptor Potential Canonical-3) channels may underlie several pathophysiological conditions -including cardiac arrhythmias. However, it is still not known if atrial and sinoatrial node cells are also involved. In this article we will first briefly review TRPC3 and IP3R signaling that relate to store/receptor-operated Ca(2+) entry (SOCE/ROCE) mechanisms and cardiac arrhythmias. We will then present some of our recent research progress in this field. Our experiments results suggest that pacing-induced AF in angiotensin II (Ang II) treated mice are significantly reduced in mice lacking the TRPC3 gene (TRPC3(-/-) mice) compared to wild type controls. We also show that pacemaker cells express TRPC3 and several other molecular components related to SOCE/ROCE signaling, including STIM1 and IP3R. Activation of G-protein coupled receptors (GPCRs) signaling that is able to modulate SOCE/ROCE and Ang II induced Ca(2+) homeostasis changes in sinoatrial complex being linked to TRPC3. The results provide new evidence that TRPC3 may play a role in sinoatrial and atrial arrhythmias that are caused by GPCRs activation.

No MeSH data available.


Related in: MedlinePlus