Although isoflurane is a known cerebral vasodilator, the mechanism of isoflurane-induced vasodilation is not clear. The purpose of this study was to investigate the effects of 2.6% isoflurane (1.2 mM) on macroscopic calcium and potassium channel currents in voltage-clamped canine middle cerebral artery cells. Cells were dialyzed with K+-glutamate solution and superfused with Tyrode's solution for measurement of potassium current (n = 20). Stepwise depolarization from a holding potential of −60 mV to beyond −30 mV elicited an outward, slowly inactivating potassium current that was reduced 50%±2% and 81%±3% (mean±SEM) in the presence of 1 mM 4-aminopyridine and 30 mM tetraethylammonium, respectively. Calcium ionophore (A23187, 10 μM) increased the potassium current by 76%±3%, suggesting calcium dependency. Isoflurane reduced the amplitude of the potassium current by 35%±4%. Calcium current was measured in cells dialyzed with solution containing 130 mM Cs+-glutamate and superfused with solution containing 10 mM BaCl2 and 135 mM tetraethylammonium to pharmacologically isolate the calcium current (n = 13). Under these conditions, progressive depolarizing steps from −60 mV elicited an inward current that was maximally activated at +20 mV and essentially eliminated by 1 μM nifedipine. This current, resembling a long-lasting (L-type) Ca2+ channel current, was reduced 40%±4% by isoflurane. The results of this study suggest that isoflurane acts directly at the vascular muscle membrane to suppress transmembrane calcium and potassium currents. The decrease in calcium current would cause vasodilation; however, the concomitant decrease in potassium current may partially antagonize the depressant effect of isoflurane mediated through calcium current reduction. These effects, in interaction with other factors, may play an important role in isoflurane-induced changes of cerebral arterial tone.
Address correspondence to Dr. Bosnjak, Medical College of Wisconsin, MFRC, Room A1000, 8701 West Watertown Plank Road, Milwaukee, WI 53226.
© 1992 International Anesthesia Research Society