Differential effects of fentanyl and morphine on intracellular Ca2+ transients and contraction in rat ventricular myocytes.
BACKGROUND
Our objective was to elucidate the direct effects of fentanyl and morphine on cardiac excitation-contraction coupling using individual, field-stimulated rat ventricular myocytes.


METHODS
Freshly isolated myocytes were loaded with fura-2 and field stimulated (0.3 Hz) at 28 degrees C. Amplitude and timing of intracellular Ca2+ concentration (at a 340:380 ratio) and myocyte shortening (video edge detection) were monitored simultaneously in individual cells. Real time Ca2+ uptake into isolated sarcoplasmic reticulum vesicles was measured using fura-2 free acid in the extravesicular compartment.


RESULTS
The authors studied 120 cells from 30 rat hearts. Fentanyl (30-1,000 nM) caused dose-dependent decreases in peak intracellular Ca2+ concentration and shortening, whereas morphine (3-100 microM) decreased shortening without a concomitant decrease in the Ca2+ transient. Fentanyl prolonged the time to peak and to 50% recovery for shortening and the Ca2+ transient, whereas morphine only prolonged the timing parameters for shortening. Morphine (100 microM), but not fentanyl (1 microM), decreased the amount of Ca2+ released from intracellular stores in response to caffeine in intact cells, and it inhibited the rate of Ca2+ uptake in isolated sarcoplasmic reticulum vesicles. Fentanyl and morphine both caused a downward shift in the dose-response curve to extracellular Ca2+ for shortening, with no concomitant effect on the Ca2+ transient.


CONCLUSIONS
Fentanyl and morphine directly depress cardiac excitation-contraction coupling at the cellular level. Fentanyl depresses myocardial contractility by decreasing the availability of intracellular Ca2+ and myofilament Ca2+ sensitivity. In contrast, morphine depresses myocardial contractility primarily by decreasing myofilament Ca2+ sensitivity.
Kanaya
N
N
Center for Anesthesiology Research, Cleveland Clinic Foundation, Ohio 44195, USA.
Zakhary
D R
DR
Murray
P A
PA
Damron
D S
DS
D008841:Actin Cytoskeleton / Q000187:drug effects; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D009020:Morphine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects
D000701:Analgesics, Opioid; D009020:Morphine; D002118:Calcium; D005283:Fentanyl