Electrophysiological effects of vasoactive intestinal peptide in rabbit atrium: a modulation of acetylcholine activity.
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.
Halimi
F
F
Department of Cardiology and INSERM U 256 Laboratory, Broussais Hospital, Paris, France.
Piot
O
O
Guize
L
L
Le Heuzey
J Y
JY
D000109:Acetylcholine / Q000502:physiology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects*; D066298:In Vitro Techniques; D008839:Microelectrodes; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014660:Vasoactive Intestinal Peptide; D014700:Verapamil; D000109:Acetylcholine