Contribution of Na+/Ca2+ exchange current to the formation of delayed afterdepolarizations in intact rat ventricular muscle.
OBJECTIVE
To evaluate the role of the Na+-Ca2+ exchange current in the induction of arrhythmias during Ca2+ waves, we investigated the relationship between Ca2+ waves and delayed afterdepolarizations (DADs) and further investigated the effect of KB-R7943, an Na+-Ca2+ exchange inhibitor, on such relationship in multicellular muscle.


METHODS
Force, sarcomere length, membrane potential, and [Ca2+]i dynamics were measured in 32 ventricular trabeculae from rat hearts. After the induction of Ca2+ waves by trains of electrical stimuli (400, 500, or 600 ms intervals) for 7.5 seconds, 23 Ca2+ waves in the absence of KB-R7943 and cilnidipine ([Ca2+]o = 2.3 +/- 0.2 mmol/L), 11 Ca2+ waves in the presence of 10 micromol/L KB-R7943 ([Ca2+]o = 2.5 +/- 0.5 mmol/L), and 8 Ca2+ waves in the presence of 1 micromol/L cilnidipine ([Ca]o = 4.1 +/- 0.3 mmol/L) were measured at a sarcomere length of 2.1 microm (23.9 +/- 0.8 degrees C).


RESULTS
The amplitude of DADs correlated with the velocity (r = 0.90) and the amplitude (r = 0.90) of Ca2+ waves. The amplitude of DADs was significantly decreased to approximately 40% of the initial value by 10 micromol/L KB-R7943.


CONCLUSIONS
These results suggest that the velocity and the amplitude of Ca2+ waves determine the formation of DADs principally through the activation of the Na+-Ca2+ exchange current, thereby inducing triggered arrhythmias in multicellular ventricular muscle.
Sugai
Yoshinao
Y
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Miura
Masahito
M
Hirose
Masanori
M
Wakayama
Yuji
Y
Endoh
Hideaki
H
Nishio
Taichi
T
Watanabe
Jun
J
ter Keurs
Henk E D J
HE
Shirato
Kunio
K
Shimokawa
Hiroaki
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D019831:Sodium-Calcium Exchanger; D013890:Thiourea; D002118:Calcium