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 Ca sensitivity under physiologic conditions in intact guinea pig beating hearts and whethe r delta (1), delta (2), and kappa opioid stimulations are related to the di rect cardiac effects of morphine. Transmural LV phasic [Ca2+](i) was measur ed from fluorescence signals at 385 nm and 456 nm. The Ca2+ transients duri ng each contraction were defined as available [Ca2+](i). The hearts were pe rfused with modified Krebs-Ringer solution containing morphine in the absen ce and presence of delta (1) (BNTX), delta (2) (NTB), and kappa (nor-BNI) a ntagonists, while developed LVP and available [Ca2+](i) were recorded. Morp hine (1 muM) decreased available [Ca2+](i) by 44 +/- 12 nM without decreasi ng developed LVP at 2.5 mM of [CaCl2](e) (P < 0.05). Morphine (1 <mu>M) cau sed a leftward shift in the curve of developed LVP as a function of availab le [Ca2+](i) (P < 0.05). BNTX (1 <mu>M), but not nor-BNI (1 muM) or NTB (0. 1 muM) blocked morphine (1 muM) effects to decrease available [Ca2+](i). Mo rphine decreases available [Ca2+](i) but not LVP, and it enhances myofilame nt Ca2+ sensitivity under physiologic conditions at clinical concentrations in intact isolated beating guinea pig hearts. The delta (1) opioid stimula tion modifies the effects of morphine on Ca transients and myofilament Ca2 sensitivity.