Glucagon-like Peptide-1 Receptor Activation Reduces Pulmonary Vein Arrhythmogenesis and Regulates Calcium Homeostasis

Figures

• 

  Figure 1. Electrophysiological effects of the glucagon-like peptide-1(GLP-1) receptor agonist on pulmonary veins (PVs). (A) Tracings of PVs (n = 8) are shown before and after treatment with GLP-1 (7-36) amide at different concentrations (1, 10, and 100 nM). (B) The graph displays the average beating rate, action potential parameters, contractile force, and diastolic tension of PVs before and after GLP-1 (7-36) amide treatment at the same concentrations (1, 10, and 100 nM). Statistical analysis reveals significant differences as indicated by * p < 0.05 and *** p < 0.005 compared to the baseline measurements.

• 

  Figure 2. Effects of inhibition of protein kinase A, Ca2+/calmodulin-dependent protein kinase II, and Na+/Ca2+ exchanger on glucagon-like peptide-1 (GLP-1) receptor agonist-related electrophysiological changes in the pulmonary veins (PVs). (A) The upper panels show tracings of PVs (n = 8) at baseline, after the treatment with H89 (10 μM), and cotreatment with H89 (10 μM) and GLP-1 (7-36) amide at 10 nM. The lower panel displays the average beating rate of PVs in response to these treatments. (B) The upper panels present tracings of PVs (n = 8) at baseline, after the treatment with KN93 (1 μM), and cotreatment with KN93 (1 μM) and GLP-1 (7-36) amide at 10 nM. The lower panel shows the average beating rate of PVs following these treatments. (C) The upper panels illustrate tracings of PVs (n = 8) at baseline, after the treatment with KB-R7943 (10 μM), and cotreatment with KB-R7943 (10 μM) and GLP-1 (7-36) amide at 10 nM. The lower panel indicates the average beating rate of PVs upon these cotreatments. Statistical analysis reveals significant differences as indicated by *** p < 0.005 compared to the baseline measurements.

• 

  Figure 3. Electrophysiological effects of glucagon-like peptide-1 (GLP-1) receptor agonist on sinoatrial node (SAN). (A) Tracings of SAN (n = 7) are displayed before and after treatment with GLP-1 (7-36) amide at different concentrations (1, 10, and 100 nM). (B) The graph presents the average beating rate of SAN before and after GLP-1 (7-36) amide treatment at the same concentrations (1, 10, and 100 nM).

• 

  Figure 4. Effects of glucagon-like peptide-1 (GLP-1) receptor agonist on L-type Ca2+ current (ICa-L) and Na+/Ca2+ exchanger current (INCX) in pulmonary vein (PV) cardiomyocytes. (A) The upper panel displays the tracings of ICa-L before and after treatment with 10 nM GLP-1 (7-36) amide in PV cardiomyocytes (n = 9). The lower panel shows the current–voltage relationship of ICa-L in response to the GLP-1 (7-36) amide treatment. Insets in the current traces depict different clamp protocols used. (B) The upper panel illustrates the tracings of INCX before and after treatment with 10 nM GLP-1 (7-36) amide in PV cardiomyocytes (n = 10). The lower panel presents the current–voltage relationship of INCX following the GLP-1 (7-36) amide treatment. Insets in the current traces show various clamp protocols used. Statistical analysis indicates significant differences as denoted by * p < 0.05 and *** p < 0.005 compared to the baseline measurements.

• 

  Figure 5. Effects of the glucagon-like peptide-1 (GLP-1) receptor agonist on Na+ current (INa) and late Na+ current (INa-Late) in pulmonary vein (PV) cardiomyocytes. (A) The upper panel presents the tracings of INa before and after treatment with 10 nM GLP-1 (7-36) amide in PV cardiomyocytes (n = 14). The lower panel shows the current–voltage relationship of INa following the GLP-1 (7-36) amide treatment. Insets in the current traces depict different clamp protocols used. (B) The upper panel illustrates the tracings of INa-Late before and after treatment with 10 nM GLP-1 (7-36) amide in PV cardiomyocytes (n = 10). The lower panel presents the current–voltage relationship of INa-Late following the GLP-1 (7-36) amide treatment. Insets in the current traces show various clamp protocols used. Statistical analysis indicates significant differences, as denoted by *** p < 0.005 compared to the baseline measurements.

• 

  Figure 6. Effects of glucagon-like peptide-1 (GLP-1) receptor agonist on sarcoplasmic reticulum (SR) Ca2+ content in pulmonary vein (PV) cardiomyocytes. Tracings of SR Ca2+ content in PV cardiomyocytes (left panel) and corresponding average data (right panel) before and after 10 nM GLP-1 (7-36) amide treatment are presented (n = 12). Statistical analysis indicates a significant difference (* p < 0.05) in SR Ca2+ content after GLP-1 (7-36) amide treatment compared to baseline levels.