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

We have examined the effects of morphine, a mu-opioid receptor agonist, on various membrane ionic currents in rat ventricular and human atrial myocyte s, using patch-clamp techniques in the whole-cell configuration. Morphine p roduced a concentration-dependent reduction in peak transient sodium curren t. When the sodium current (I-Na) was evoked at 5-s intervals the estimated IC50 for morphine was approximately 30 mu mol litre(-1). Morphine 10 mu mo l litre(-1) inhibited I-Na with a 5-mV shift in the potential-dependent ina ctivation curve to negative potentials and retarded the I-Na recovery rate from the inactivated state. Use-dependent I-Na block was not observed when I-Na was elicited at frequencies varying from 0.2 to 20 Hz. Morphine did no t significantly affect the inward calcium current (I-Ca), transient outward current (I-to) or the inwardly rectifying potassium current (I-K1) at a co ncentration of 30 mu mol litre(-1) The inhibitory effect of morphine on I-N a could not be prevented or reversed by treatment with the opioid antagonis t naloxone. Therefore, we suggest that morphine can directly inhibit the Na + inward current and bind to inactivated Na+ channels.