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  • K R Courtney
  • 1975
A new lidocaine derivative (Astra, GEA 968) depresses excitability of myelinated frog nerve in a manner which depends upon the rate of use of the nerve. This phenomenon has been shown, under voltage clamp conditions, to involve "frequency-" or "use-dependent" inhibition of the transient inward sodium currents at the node of Ranvier. With 0.6 mM GEA 968 in(More)
  • K R Courtney
  • 1980
Different local anesthetic drug structures differ significantly in their capabilities for producing frequency (f)-dependent sodium channel block. Voltage-clamped frog myelinated nerve preparations have been utilized in order to investigate structure-activity relations for several modes of local anesthetic drug action, including the kinetics of f-dependent(More)
We have looked at several anticonvulsant drugs regarding their potency for basal block of sodium channels in both skeletal muscle and myelinated nerve preparations under voltage clamp conditions. There is an inverse relationship observed between the half-blocking concentration of each drug and its lipid distribution coefficient. Furthermore the(More)
Excitable membranes exposed to sodium channel blocking agents (D; local anesthetics and antiarrhythmic drugs) show a progressive reduction of peak sodium current when repetitively depolarized (use dependence). Thus, with repetitive excitation, use dependence reflects a net rightward shift in the balance between unblocked channels (U) and blocked channels(More)
  • K R Courtney
  • 1987
Different class 1 antiarrhythmic drugs have differing capabilities for producing a rate-dependent modulation of cardiac excitability. Structural hypotheses regarding these drug actions, both in terms of their widely differing abilities for blocking myocardial sodium channels during individual action potentials and their associated repriming kinetics, have(More)
The influence that drug size has on the rate of recovery of sodium channels in heart tissue has been reexamined. A drug dimension that looks at the end-on view of the molecule provides a substantially better explanation for the size dependence of repriming kinetics than does molecular weight. A quantitative model for the recovery time is provided that(More)
Muscle contraction can introduce artifact in attempted optical measurements of the action potential in heart tissue stained with voltage-sensitive dyes. Using rabbit sinus node and atrial tissue in vitro, we found that the voltage-sensitive part of the optical signal remains relatively unchanged by variations in the rate of external stimulation or by the(More)