In vitro electrophysiologic effects of morphine in rabbit ventricular myocytes.
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 microM significantly prolonged cardiac action potential, and at 0.1 and 1 microM slightly but significantly hyperpolarized the resting membrane potential. In addition, morphine at 0.1 microM 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 microM naltrindole (a selective delta-opioid receptor antagonist) or 5 microM norbinaltorphimine (a selective kappa-opioid receptor antagonist) prevented the increase in ICa.L induced by morphine, but 5 microM CTOP (a selective mu-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 delta- and kappa-opioid receptors. It also hyperpolarizes cardiac resting membrane potential by increasing IK1, which is not mediated by opioid receptors.
Xiao
Guo-Sheng
GS
Department of Physiology, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China.
Zhou
Jing-Jun
JJ
Wang
Guan-Ying
GY
Cao
Chun-Mei
CM
Li
Gui-Rong
GR
Wong
Tak-Ming
TM
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole; D002118:Calcium