Interaction of intravenous anesthetics with human neuronal potassium currents in relation to clinical concentrations

Background: Neuronal voltage-dependent potassium (K) currents are crucial f or various cellular functions, such as the integration of temporal informat ion in the central nervous system. Data for the effects of intravenous anes thetics on human neuronal K currents are limited. It was the authors' aim t o evaluate the concentration-related effects of three opioids (fentanyl, al fentanil, sufentanil) and seven nonopioids (thiopental, pentobarbital, meth ohexital, propofol, ketamine, midazolam, droperidol) used in clinical anest hesia on neuronal voltage-dependent K currents of human origin. Method: K currents were measured in SH-SY5Y cells using the whole cell patc h-clamp technique. Currents were elicited by step depolarization from a hol ding potential of -80 to -50 mV through +90 mV, and their steady state ampl itudes were determined. Results: All drugs inhibited the K currents in a concentration-dependent an d reversible manner. Because time dependence of inhibition differed among t he drugs, effects were measured after 54-64 ms of the test pulse. The IC50 values (concentration of half-maximal inhibition) for current suppression r anged from 7 mu M for sufentanil to 2 mM for pentobarbital. Suppression of the K currents by the opioids occurred at 10-fold lower IC50 values (concen tration of half-maximal inhibition) than that by the barbiturates. As estim ated from the concentration-response curves, K-current suppression at clini cal concentrations would be less than 0.1% for the opioids and approximatel y 3% for the other drugs. Conclusions: Effects of intravenous anesthetics on voltage-dependent K curr ents occur at clinical concentrations. The IC50 values for current inhibiti on of the nonopioid anesthetics correlated with these concentrations (r = 0 .95). The results suggest that anesthetic drug action on voltage-dependent K currents may contribute to clinical effects or side effects of intravenou s anesthetics.