In vitro electrophysiologic effects of morphine in rabbit ventricular myocytes

Abstract

Background: Morphine is widely used in patients undergoing surgical operations and is also reported to mediate cardioprotection of preconditioning. The current study determined effects of morphine at therapeutic to pharmacologic concentrations on cardiac action potential, L-type Ca2+ current (ICa.L), delayed rectifier K+ current (IK), and inward rectifier K+ current (IK1) in isolated rabbit ventricular myocytes. Methods: Ventricular myocytes were enzymatically isolated from rabbit hearts. Action potential and membrane currents were recorded in current and voltage clamp modes. Results: Morphine at concentrations from 0.01 to 1 μM significantly prolonged cardiac action potential, and at 0.1 and 1 μM slightly but significantly hyperpolarized the resting membrane potential. In addition, morphine at 0.1 μM significantly augmented ICa.L (at + 10 mV) from 5.9 ± 1.9 to 7.3 ± 1.7 pA/pF (by 23%; P < 0.05 vs. control) and increased IK1 (at -60 mV) from 2.8 ± 1.0 to 3.5 ± 0.9 pA/pF (by 27%; P < 0.05 vs. control). Five μM naltrindole (a selective δ-opioid receptor antagonist) or 5 μM norbinaltorphimine (a selective κ-opioid receptor antagonist) prevented the increase in ICa.L induced by morphine, but 5 μM CTOP (a selective μ-opioid receptor antagonist) did not. The three types of opioid antagonists did not affect the augmentation of IK1 by morphine. Morphine had no effect on IK. Conclusions: These results indicate that morphine prolongs action potential duration by increasing ICa.L, an effect mediated by δ- and κ-opioid receptors. It also hyperpolarizes cardiac resting membrane potential by increasing IK1, which is not mediated by opioid receptors. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.