Selective Inhibition of Pulmonary Vein Excitability by Constitutively Active GIRK Channels Blockade in Rats
Abstract
:1. Introduction
2. Results
2.1. Differential Effects of Tertiapin-Q upon the PV and the LA in Presence of Acetylcholine
2.2. Direct Effects of Tertiapin-Q upon the PV and the LA
2.3. Reversal of Tertiapin-Q Effects upon the PV and the LA
2.3.1. Reversal of Tertiapin-Q Effects by Acetylcholine
2.3.2. Reversal of Tertiapin-Q Effects through Kir6.2 Channel Activation
2.4. Selectivity of Tertiapin-Q against GIRK Channels in PV and LA Cardiomyocytes
2.5. Constitutively Active GIRK Channels in PV and LA Cardiomyocytes
3. Discussion
4. Materials and Methods
4.1. Intracellular Microelectrode Recordings
4.2. Whole Cell Patch Clamp Experiments
4.3. Preparation of Tissue Homogenates and Western Blotting
4.4. Statistical Analysis
4.5. Chemicals
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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TQ | TQ+ 10−7 M ACh | TQ+ 10−6 M ACh | 10−6 M ACh | ||||
---|---|---|---|---|---|---|---|
PV | |||||||
DMP | −55.3 ± 1.8 | p = 0.145 | −58.7 ± 1.3 | p < 0.001 | −70.9 ± 2.3 | p = 0.012 | −77.2 ± 1.0 |
AP peak | −49.2 ± 1.3 | p = 0.988 | −49.2 ± 2.5 | p < 0.001 | 5.6 ± 4.0 | p < 0.001 | 23.4 ± 1.3 |
LA | |||||||
DMP | −72.7 ± 1.3 | p = 0.895 | −72.9 ± 1.1 | p = 0.959 | −72.8 ± 1.6 | p = 0.042 | −76.3 ± 0.7 |
AP peak | 19.0 ± 1.2 | p = 0.417 | 17.7 ± 1.0 | p = 0.401 | 18.9 ± 0.9 | p = 0.471 | 17.7 ± 1.1 |
Basal | 10−7 M ACh | 10−6 M ACh | |||
---|---|---|---|---|---|
Control (n = 10) | 38.4 ± 0.9 | p < 0.001 | 29.9 ± 1.2 | p < 0.001 | 19.3 ± 1.3 |
p < 0.001 | p < 0.001 | p < 0.001 | |||
Tertiapin-Q (n = 9) | 52.8 ± 1.6 | p = 0.002 | 45.0 ± 1.0 | p = 0.001 | 39.6 ± 1.0 |
Basal | P1075 | ||
---|---|---|---|
Control (n = 9) | 42.5 ± 2.1 | p < 0.001 | 11.5 ± 1.2 |
p < 0.001 | p = 0.020 | ||
Tertiapin-Q (n = 7) | 56.4 ± 2.1 | p < 0.001 | 16.3 ± 1.5 |
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Findlay, I.; Pasqualin, C.; Yu, A.; Maupoil, V.; Bredeloux, P. Selective Inhibition of Pulmonary Vein Excitability by Constitutively Active GIRK Channels Blockade in Rats. Int. J. Mol. Sci. 2023, 24, 13629. https://doi.org/10.3390/ijms241713629
Findlay I, Pasqualin C, Yu A, Maupoil V, Bredeloux P. Selective Inhibition of Pulmonary Vein Excitability by Constitutively Active GIRK Channels Blockade in Rats. International Journal of Molecular Sciences. 2023; 24(17):13629. https://doi.org/10.3390/ijms241713629
Chicago/Turabian StyleFindlay, Ian, Côme Pasqualin, Angèle Yu, Véronique Maupoil, and Pierre Bredeloux. 2023. "Selective Inhibition of Pulmonary Vein Excitability by Constitutively Active GIRK Channels Blockade in Rats" International Journal of Molecular Sciences 24, no. 17: 13629. https://doi.org/10.3390/ijms241713629