Sodium/calcium exchange contributes to contraction and relaxation in failed human ventricular myocytes.
Defects in myocyte contraction and relaxation are key features of human heart failure. Sodium/calcium exchanger-mediated contribution to contraction and relaxation were separated from other mechanisms [L-type calcium current, sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase] based on voltage, temperature, and selective blockers. Rod-shaped left ventricular myocytes were isolated from failed human explants (n = 29) via perfusion with collagenase-containing Krebs solution. Action potentials using perforated patch and contractions using an edge detector were recorded at 0.5-1.5 Hz in Tyrode solution at 25 degrees C and 37 degrees C. Contraction duration was dependent on action potential (AP) duration at 37 degrees C but not at 25 degrees C, suggesting the role of the exchanger in relaxation and linking myocyte relaxation to the repolarization phase of the AP. Voltage-clamp experiments from -50 to +10 mV for 1,500 ms in Tyrode or Na(+)- and K(+)-free solutions after conditioning pulses triggered biphasic contractions that included a rapid SR-mediated component and a slower voltage-dependent exchanger-mediated component. We used thapsigargin to block the SR, which eliminated the rapid component, and we used an exchanger blocker, Kanebo 7943, which eliminated the slow component. The exchanger was shown to contribute to contraction through reverse-mode exchange, as well as to play a key role in relaxation of human ventricular myocytes.
Gaughan
J P
JP
Departments of Physiology and Cardio-Thoracic Surgery, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. jgaughan<@pond.com>
Furukawa
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S
Jeevanandam
V
V
Hefner
C A
CA
Kubo
H
H
Margulies
K B
KB
McGowan
B S
BS
Mattiello
J A
JA
Dipla
K
K
Piacentino
V
V
Li
S
S
Houser
S R
SR
D000200:Action Potentials / Q000187:drug effects; D002303:Cardiac Output, Low / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000473:pathology; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D013696:Temperature; D019284:Thapsigargin / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D016276:Ventricular Function
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D004791:Enzyme Inhibitors; D019831:Sodium-Calcium Exchanger; D019284:Thapsigargin; D013890:Thiourea