Morphine Enhances Myofilament Ca2+ Sensitivity in Intact Guinea Pig Beating Hearts

We investigated whether morphine alters intracellular Ca2+ concentration ([Ca2+]i), left ventricular pressure (LVP), and myofilament Ca2+ sensitivity under physiologic conditions in intact guinea pig beating hearts and whether δ1, δ2, and κ opioid stimulations are related to the direct cardiac effects of morphine. Transmural LV phasic [Ca2+]i was measured from fluorescence signals at 385 nm and 456 nm. The Ca2+ transients during each contraction were defined as available [Ca2+]i. The hearts were perfused with modified Krebs-Ringer solution containing morphine in the absence and presence of δ1 (BNTX), δ2 (NTB), and κ (nor-BNI) antagonists, while developed LVP and available [Ca2+]i were recorded. Morphine (1 μM) decreased available [Ca2+]i by 44 ± 12 nM without decreasing developed LVP at 2.5 mM of [CaCl2]e (P < 0.05). Morphine (1 μM) caused a leftward shift in the curve of developed LVP as a function of available [Ca2+]i (P < 0.05). BNTX (1 μM), but not nor-BNI (1 μM) or NTB (0.1 μM) blocked morphine (1 μM) effects to decrease available [Ca2+]i. Morphine decreases available [Ca2+]i but not LVP, and it enhances myofilament Ca2+ sensitivity under physiologic conditions at clinical concentrations in intact isolated beating guinea pig hearts. The δ1 opioid stimulation modifies the effects of morphine on Ca2+ transients and myofilament Ca2+ sensitivity.