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Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013
Electrophysiological effects of vasoactive intestinal peptide in rabbit atrium: a modulation of acetylcholine
1Department of Cardiology and INSERM U 256 Laboratory, Broussais Hospital, Paris, France.
Abstract:
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid peptide partially co-secreted with acetylcholine (Ach) in the atrial tissue. We studied the electrophysiological effects of VIP and Ach in rabbit isolated right atrium by the microelectrode technique. After a 10-min superfusion with VIP, action potential duration at 90% of repolarization (APD90) was lengthened by 23% (P = 0.01) at the concentration of 10(-8) M (n = 10), by 22% (P = 0.004) at 10(-7) M (n = 10) and by 33% (P = 0.03) at 2 x 10(-7) M (n = 5). To explain this APD90 lengthening, we performed 10 other experiments with VIP 10(-7) M, including five preparations pretreated with verapamil (10(-6) M) for 20 min. In the five preparations not pretreated, APD90 was increased by 27% (P = 0.04) after 10 min but remained unchanged in those previously exposed to verapamil, suggesting that VIP is a calcium current activator. Ach (1.4 x 10(-5) M) was superfused in five other experiments and we observed a 31% decrease in APD90 (P= 0.04) at 10 min. After washout, we simultaneously perfused, on the same preparations, Ach (same concentration) and VIP (10(-7) M) for 10 min. The decrease in APD90 (19%) was no longer significant. VIP (2 x 10(-7) M) lengthened cellular effective refractory periods (ERP) by 26% (P = 0.04) after 10 min (n = 5), whereas Ach (1.4 x 10(-5) M) decreased ERP by 33% (P = 0.04) at 10 min (n = 5). In conclusion, VIP lengthens atrial APD90, which may be the result of calcium current activation. In addition, VIP could modulate Ach activity in limiting APD90 shortening in the presence of Ach and because of its opposite effect on atrial ERP. Therefore, VIP could be involved in the control of vagal atrial arrhythmias.
Insights
Vasoactive Intestinal Peptide (VIP) lengthens atrial action potential duration by activating calcium currents. VIP also modulates acetylcholine (Ach) effects, potentially controlling vagal atrial arrhythmias.
Area of Science:
- Cardiovascular Physiology
- Neuroendocrinology
Background:
- Vasoactive Intestinal Peptide (VIP) is co-secreted with acetylcholine (Ach) in atrial tissue.
- Understanding the electrophysiological roles of VIP and Ach is crucial for cardiac function.
Purpose of the Study:
- To investigate the electrophysiological effects of VIP and Ach on rabbit isolated right atrium.
- To elucidate the mechanism of VIP-induced action potential duration lengthening.
- To determine the interaction between VIP and Ach in modulating atrial electrophysiology.
Main Methods:
- Microelectrode technique used on isolated rabbit right atrium.
- Superfusion with varying concentrations of VIP and Ach.
- Experiments involving verapamil pretreatment to assess calcium current involvement.
- Simultaneous perfusion of VIP and Ach to study their combined effects.
Main Results:
- VIP significantly lengthened action potential duration at 90% repolarization (APD90) in a dose-dependent manner.
- VIP-induced APD90 lengthening was abolished by verapamil, indicating calcium current activation.
- Ach decreased APD90, while VIP counteracted this shortening effect when co-administered.
- VIP lengthened effective refractory periods (ERP), whereas Ach decreased ERP.
Conclusions:
- VIP lengthens atrial APD90, likely through calcium current activation.
- VIP can modulate Ach activity, potentially mitigating Ach-induced APD90 shortening.
- VIP's opposing effects on atrial ERP compared to Ach suggest a role in controlling vagal atrial arrhythmias.
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