The potassium conductance of the resting squid axon and its blockage by clinical concentrations of general anaesthetics.

Abstract

SUMMARY1. The effects of some neutral clinical and experimental general anaesthetics on the resting potential of normal squid axons and squid axons exposed to tetrodotoxin and 3,4-diaminopyridine have been studied.2. Depolarizations of 1-4 mV were produced by all the anaesthetics at 'clinical' concentrations in the normal axon. Larger depolarizations (5-11 mV) were produced by the same anaesthetic concentrations in axons exposed to tetrodotoxin and 3,4-diaminopyridine.3. The conductance of axons exposed to tetrodotoxin and either tetraethylammonium or 3,4-diaminopyridine in zero Na+, 430 mM-K+ artificial sea water was examined by voltage clamp and AC bridge techniques.4. The evidence that this conductance is due predominantly to K+ is discussed. 5. Pre-pulse protocols under voltage clamp have been used to show that part of this conductance arises from the incompletely blocked delayed rectifier.6. Substantial reductions in this conductance are produced by anaesthetics at clinical' concentrations.7. It is concluded that there is a component of the K+ conductance of the resting squid axon other than the Hodgkin-Huxley delayed rectifier which is extremely sensitive to anaesthetics and which to an appreciable extent determines the resting potential.

Local anesthetics potently block a potential insensitive potassium channel in myelinated nerve.

“…According to Drachman and Strichartz (1991), conduction block is facilitated under depolarization. Both depolarizing and hyperpolarizing changes of the membrane potential as induced by anesthetics have been reported earlier Haydon et al, 1988;MacIver and Kendig, 1991). In our study with amphibian myelinated nerve, flicker K + channels are more frequently found in thin nerve fibers ( < 5 Ixm) which in general conduct pain.…”

“…The contribution of fast K + channel block to conduction block of the fiber is small because these channels are mainly responsible for the fast repolarization of the action potential, as can be shown in computer simulations (Ritchie and Stagg, 1982;Vogel and Schwarz, 1995). The resting potential which to some extent may be generated by voltage-independent potassium permeability is slightly depolarized by (general) anesthetics in the squid axon (Urban and Haydon, 1987;Haydon, Requena, and Simon, 1988; whereas hippocampal CA1 neurones are hyperpolarized (MacIver and Kendig, 1991). Our investigations describe the blockade of voltage-independent K + channels in peripheral nerve membrane by several local anesthetics.…”

Excitation of the squid giant axon by general anaesthetics.

“…Quantitative calculations of the resting potential changes for comparison with experiment have been made based on the changes in K+ conductance determined in the preceding paper (Haydon, Requena & Simon, 1988) and changes in the Hodgkin-Huxley parameters of the Na+ and delayed-rectifier K+ currents.…”

“…More likely it arises because, at the concentrations used, the effect on the resting potential is near saturation (see Fig. 3 of Haydon et al 1988) whereas the effects on the Na+ channel are small and the concentration dependence still in the linear region. This being so, it is easy to see that the resting potential will reach its half-final value before the Na+ channel activation does.…”

“…The changes were invariably monotonic, in contrast to the variations in minimum stimulus. The origins of the resting potential changes have been considered in the preceding paper (Haydon et al 1988). …”