Modulation of Spontaneous Action Potential Rate by Inositol Trisphosphate in Myocytes from the Rabbit Atrioventricular Node
Abstract
:1. Introduction
2. Materials and Methods
2.1. AVN Cell Isolation
2.2. Electrophysiological Recording
2.3. Calcium Imaging
2.4. Flash Photolysis
2.5. Immunohistochemistry
2.6. Experimental Compounds
2.7. Data Analysis and Statistics
3. Results
3.1. Immunohistochemistry
3.2. Effects of Cell Permeant IP3: Bt3-(1,4,5)IP3-AM
3.3. IP3-R Inhibition with Xestospongin C
3.4. Effect of Photoreleased IP3 on AP Rate
3.5. Effects of 2-APB
3.6. Effect of Photoreleased IP3 under AP Voltage Clamp
4. Discussion
4.1. IP3-R2s in the Rabbit AVN
4.2. ICa,L and IKr Inhibition by 2-APB
4.3. Evidence for Constitutive and IP3-R Activity in Modulating AVN Cell Rate
4.4. Limitations, Future Work and Conclusions
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Control | 10 µM Bt3-(1,4,5)IP3-AM |
---|---|---|
Spontaneous AP rate (beats s−1) (Percentage increase %) | 2.85 ± 0.17 | 3.96 ± 0.21 ** (40.5 ± 5.7%) |
Slope of pacemaker diastolic depolarization (mV s−1) | 64.6 ± 8.4 | 102.3 ± 10.6 * |
Maximal upstroke velocity (Vmax, V s−1) | 4.67 ± 0.80 | 3.89 ± 1.14 |
Maximal repolarization velocity (Vrep, V s−1) | −1.22 ± 0.08 | −1.09 ± 0.08 |
AP duration at 50% repolarization (APD50, ms) | 77.4 ± 3.5 | 73.3 ± 3.8 |
Maximal diastolic potential (MDP, mV) | −51.8 ± 2.8 | −49.4 ± 1.9 |
Overshoot (mV) | 20.6 ± 2.1 | 11.6 ± 2.9 * |
AP amplitude (mV) | 71.5 ± 4.0 | 61.0 ± 4.4 |
Parameter | Untreated Cells | Xestospongin C (Start of Recording) | Xestospongin C (~1 min of Recording) |
---|---|---|---|
Spontaneous AP rate (beats s−1) (Percentage decrease %) | 2.85 ± 0.17 | 2.63 ± 0.14 (7.7%, vs. untreated cells) | 1.94 ± 0.17 * ## (23.1 ± 8.7%, vs. Xe-C At Start) |
Slope of pacemaker diastolic depolarization (mV s−1) | 64.6 ± 8.4 | 97.8 ± 13.2 | 51.0 ± 5.2 ** |
Maximal upstroke velocity (Vmax, V s−1) | 4.67 ± 0.80 | 8.66 ± 1.30 | 8.47 ± 1.42 # |
Maximal repolarization velocity (Vrep, V s−1) | −1.22 ± 0.08 | −1.61 ± 0.16 | −1.49 ± 0.12 |
AP duration at 50% repolarization (APD50, ms) | 77.4 ± 3.5 | 84.7 ± 3.5 | 83.5 ± 3.1 |
Maximal diastolic potential (MDP, mV) | −51.8 ± 2.8 | −53.4 ± 2.1 | −57.6 ± 2.3 ** |
Overshoot (mV) | 20.6 ± 2.1 | 31.8 ± 2.2 | 30.5 ± 2.2 ## |
AP amplitude (mV) | 71.5 ± 4.0 | 85.2 ± 4.0 | 88.1 ± 4.3 # |
Parameter | Control | With UV Excitation of Caged IP3 |
---|---|---|
Spontaneous AP rate (beats s−1) (Percentage increase %) | 2.30 ± 0.37 | 2.90 ± 0.36 * (32.1 ± 9.5%) |
Slope of pacemaker diastolic depolarization (mV s−1) | 73.4 ± 17.6 | 110.5 ± 14.0 * |
Maximal upstroke velocity (Vmax, V s−1) | 6.55 ± 1.49 | 7.73 ± 1.66 |
Maximal repolarization velocity (Vrep, V s−1) | −1.86 ± 0.15 | −1.82 ± 0.17 |
AP duration at 50% repolarization (APD50, ms) | 69.1 ± 5.1 | 71.0 ± 4.5 |
Maximal diastolic potential (MDP, mV) | −65.8 ± 1.9 | −65.3 ± 2.3 |
Overshoot (mV) | 26.1 ± 4.5 | 27.9 ± 4.4 |
AP amplitude (mV) | 91.9 ± 4.5 | 93.2 ± 4.3 |
Parameter | Control | 10 μM 2-APB | Control | 1 μM 2-APB |
---|---|---|---|---|
Spontaneous AP rate (beats s−1) (Percentage decrease %) | 3.10 ± 0.36 | 2.28 ± 0.37 ** (28.0 ± 4.3%) | 2.78 ± 0.22 | 2.07 ± 0.22 ** (25.2 ± 6.2%) |
Slope of pacemaker diastolic depolarization (mV s−1) | 79.2 ± 18.9 | 24.6 ± 7.7 ** | 82.0 ± 9.2 | 34.8 ± 3.6 ** |
Maximal upstroke velocity (Vmax, V s−1) | 5.50 ± 1.05 | 0.78 ± 0.12 ** | 7.03 ± 2.14 | 4.55 ± 1.54 ** |
Maximal repolarization velocity (Vrep, V s−1) | −1.34 ± 0.11 | −0.66 ± 0.05 ** | −2.49 ± 0.50 | −2.43 ± 0.51 |
AP duration at 50% repolarization (APD50, ms) | 68.4 ± 3.1 | 117.8 ± 11.6 ** | 75.2 ± 5.7 | 90.7 ± 5.0 ** |
Maximal diastolic potential (MDP, mV) | −51.8 ± 2.5 | −38.9 ± 3.4 ** | −62.7 ± 2.8 | −58.2 ± 3.5 * |
Overshoot (mV) | 24.5 ± 3.5 | −0.19 ± 3.1 ** | 23.0 ± 4.3 | 13.6 ± 5.2 ** |
AP amplitude (mV) | 76.3 ± 5.5 | 38.7 ± 3.0 ** | 85.5 ± 6.6 | 71.8 ± 8.4 ** |
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Cheng, H.; Kong, C.H.T.; James, A.F.; Cannell, M.B.; Hancox, J.C. Modulation of Spontaneous Action Potential Rate by Inositol Trisphosphate in Myocytes from the Rabbit Atrioventricular Node. Cells 2024, 13, 1455. https://doi.org/10.3390/cells13171455
Cheng H, Kong CHT, James AF, Cannell MB, Hancox JC. Modulation of Spontaneous Action Potential Rate by Inositol Trisphosphate in Myocytes from the Rabbit Atrioventricular Node. Cells. 2024; 13(17):1455. https://doi.org/10.3390/cells13171455
Chicago/Turabian StyleCheng, Hongwei, Cherrie H. T. Kong, Andrew F. James, Mark B. Cannell, and Jules C. Hancox. 2024. "Modulation of Spontaneous Action Potential Rate by Inositol Trisphosphate in Myocytes from the Rabbit Atrioventricular Node" Cells 13, no. 17: 1455. https://doi.org/10.3390/cells13171455