The effects of halothane and isoflurane on slowly inactivating sodium current in canine cardiac Purkinje cells.
The effects of halothane (0.45 and 0.9 mM, equivalent to 0.7 and 1.5 vol%, respectively) and isoflurane (0.56 and 1.23 mM, equivalent to 0.9 and 2.0 vol%) on slowly inactivating Na+ current were examined by whole-cell voltage-clamp techniques. This approach allows evaluation of the role of anesthetic inhibition of inward Na+ current on the action potentials of canine Purkinje fibers isolated from the false tendons. Cells were superfused with Tyrode's solution containing nifedipine and Ni2+ to block Ca2+ channel currents and internally dialyzed with Cs+ to block outward K+ currents. Veratridine (0.5 microM) was used throughout the experiments to enhance the slow Na+ current. Na+ current was elicited by depolarizing pulses from a holding potential of -100 mV to stepwise (10 mV increments) more positive membrane potentials and measured at 200 ms after initiation of the voltage pulse before, during, and after exposure to anesthetics. Slowly inactivating Na+ current showed threshold activation at -80 mV and peak activation around -55 to -40 mV. This current was abolished by 5 microM tetrodotoxin, showing the characteristic feature of Na+ channel current. Halothane and isoflurane depressed the amplitude of slowly inactivating Na+ current in a concentration-dependent manner and did not shift the current-voltage relationship for slow Na+ current activation. There was no significant difference between the sensitivities of slow Na+ current to halothane or isoflurane at equianesthetic concentrations. Inhibition of slow inward Na+ current may contribute to the marked decrease of action potential duration produced by volatile anesthetics in false tendon Purkinje fibers but does not account for the larger decreases of duration produced by isoflurane than halothane.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
H
H
Eskinder
F D
FD
Supan
L A
LA
Turner
J P
JP
Kampine
Z J
ZJ
Bosnjak
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004285:Dogs; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011690:Purkinje Fibers / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects*
D015222:Sodium Channels; D007530:Isoflurane; D011188:Potassium; D006221:Halothane