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British Journal of Anaesthesia, Vol 81, Issue 6 925-931, Copyright © 1998 by The Board of Management and Trustees of the British Journal of Anaesthesia


LABORATORY INVESTIGATIONS

Opioid receptor independent effects of morphine on membrane currents in single cardiac myocytes

C. F. Hung, C. H. Tsai and M. J. Su
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan

We have examined the effects of morphine, a mu-opioid receptor agonist, on various membrane ionic currents in rat ventricular and human atrial myocytes, using patch-clamp techniques in the whole-cell configuration. Morphine produced a concentration-dependent reduction in peak transient sodium current. When the sodium current (INa) was evoked at 5-s intervals the estimated IC50 for morphine was approximately 30 microgramsmol litre-1. Morphine 10 microgramsmol litre-1 inhibited INa with a 5-mV shift in the potential-dependent inactivation curve to negative potentials and retarded the INa recovery rate from the inactivated state. Use- dependent INa block was not observed when INa was elicited at frequencies varying from 0.2 to 20 Hz. Morphine did not significantly affect the inward calcium current (ICa), transient outward current (Ito) or the inwardly rectifying potassium current (IK1) at a concentration of 30 microgramsmol litre-1. The inhibitory effect of morphine on INa could not be prevented or reversed by treatment with the opioid antagonist naloxone. Therefore, we suggest that morphine can directly inhibit the Na+ inward current and bind to inactivated Na+ channels.
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