Morphine enhances myofilament CA(2+) sensitivity in intact guinea pig beating hearts.
We investigated whether morphine alters intracellular Ca(2+) concentration ([Ca(2+)](i)), left ventricular pressure (LVP), and myofilament Ca(2+) sensitivity under physiologic conditions in intact guinea pig beating hearts and whether delta(1), delta(2), and kappa opioid stimulations are related to the direct cardiac effects of morphine. Transmural LV phasic [Ca(2+)](i) was measured from fluorescence signals at 385 nm and 456 nm. The Ca(2+) transients during each contraction were defined as available [Ca(2+)](i). The hearts were perfused with modified Krebs-Ringer solution containing morphine in the absence and presence of delta(1) (BNTX), delta(2) (NTB), and kappa (nor-BNI) antagonists, while developed LVP and available [Ca(2+)](i) were recorded. Morphine (1 microM) decreased available [Ca(2+)](i) by 44 +/- 12 nM without decreasing developed LVP at 2.5 mM of [CaCl(2)](e) (P < 0.05). Morphine (1 microM) caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). BNTX (1 microM), but not nor-BNI (1 microM) or NTB (0.1 microM) blocked morphine (1 microM) effects to decrease available [Ca(2+)](i). Morphine decreases available [Ca(2+)](i) but not LVP, and it enhances myofilament Ca(2+) sensitivity under physiologic conditions at clinical concentrations in intact isolated beating guinea pig hearts. The delta(1) opioid stimulation modifies the effects of morphine on Ca(2+) transients and myofilament Ca(2+) sensitivity.


CONCLUSIONS
Morphine modifies myofilament Ca(2+) sensitivity and Ca(2+) transients in guinea pig hearts at concentrations that are clinically relevant.
Department of Anesthesiology, Sapporo Medical University School of Medicine, Japan. ynakae@mcw.edu
Y
Y
Nakae
S
S
Fujita
A
A
Namiki
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000502:physiology; D013045:Species Specificity; D016277:Ventricular Function, Left / Q000187:drug effects
D009294:Narcotics; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D009020:Morphine; D002118:Calcium