A SIMPLIFIED MODEL OF PROPAGATION AND DISSIPATION OF EXCITATION FRONTS

An excitation wave in nerve or cardiac tissue may fail to propagate if the temporal gradient of the transmembrane voltage at the front becomes too small to excite the tissue ahead of it. A simplified mathematical model is suggested, that reproduces this phenomenon and has exact traveling front solutions. The spectrum of possible propagation speeds is bounded from below. This causes a front to dissipate if it is not allowed to propagate quickly enough. A crucial role is played by the Na inactivation gates, even if their dynamics are by an order of magnitude slower than the dynamics of the voltage.

Slow inhibition of Na+ current in crayfish axons by 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of an ant venom alkaloid

2,5-Dialkylpyrrolidines present in the venom of ants from the genus Monomorium are natural insecticides causing a flaccid paralysis. The mechanism of action of 2-(1non-8enyl)-5-(1non-8enyl)pyrrolidine (Pyr9), a synthetic derivative of 2,5-dialkylpyrrolidines, has been investigated in vitro on preparations of the ventral nerve cord of the crayfish Procambarus clarkii. Our results clearly indicate that Pyr9 blocks spike conduction without affecting the resting potential. Voltage-clamp experiments carried out on axons demonstrate that this blockade is due to a dual expression of Na+ current inhibition: a tonic inhibition developing slowly (90 % of inhibition within 20 min for a Pyr9 concentration of 50 µmol l-1) and independently of stimulation, and a phasic inhibition developing during repetitive stimulation (5 Hz), the accumulation kinetics of which is 0.072 pulse-1 at 5 Hz, according to the Courtney model. These findings suggest that tonic and phasic inhibition are due to different mechanisms. In addition, Pyr9 induces a shift of the Na+ inactivation curve towards more hyperpolarized potentials, which is in agreement with a higher affinity of Pyr9 for inactivated than for resting Na+ channels.

Effect of sea anemone toxins on the sodium inactivation process in crayfish axons.

The effect of sea anemone toxins from Parasicyonis actinostoloides and Anemonia sulcata on the Na conductance in crayfish giant axons was studied under voltage-clamp conditions. The toxin slowed the Na inactivation process without changing the kinetics of Na activation or K activation in an early stage of the toxin effect. An analysis of the Na current profile during the toxin treatment suggested an all-or-none modification of individual Na channels. Toxin-modified Na channels were partially inactivated with a slower time course than that of the normal inactivation. This slow inactivation in steady state decreased in its extent as the membrane was depolarized to above -45 mV, so that practically no inactivation occurred at the membrane potentials as high as +50 mV. In addition to inhibition of the normal Na inactivation, prolonged toxin treatment induced an anomalous closing in a certain population of Na channels, indicated by very slow components of the Na tail current. The observed kinetic natures of toxin-modified Na channels were interpreted based on a simple scheme which comprised interconversions between functional states of Na channels. The voltage dependence of Parasicyonis toxin action, in which depolarization caused a suppression in development of the toxin effect, was also investigated.