Isoflurane sensitivity of Drosophila axons is enhanced in an Na+ channel mutant

摘要

I studied the role of the voltage-gated Na~+ current, I_(NaV), in mediating the effects of general anesthetics, using neuromuscular electrophysiology and computer simulations. Isoflurane-induced slowing of action potential propagation was enhanced in para~(tsl), a hypomorphic mutant of the voltage-gated Na~+ channel, providing a physiological correlate of behavioral hypersensitivity. Simulating anesthetic action as inhibition of voltage-dependent Na~+ (I_(NaV)) slowed spike conduction. Fifty percent reduction of I_(NaV), simulating a para mutation, enhanced the simulated effect of anesthetic. However, the simulated para mutation also enhanced the anesthetic effect when modeled as K~+ currents.