Analysis of the sensitizing effect of veratrum alkaloids to potassium on frog muscle.

1. The sensitizing effect of veratrum alkaloids to potassium is not specific. Reducing the concentration of chloride in Ringer's solution, or treating the muscle with nicotine in a concentration close to threshold after pretreatment with subliminal concentration of cevadine result in a marked mechanical response of the muscle. However, cevadine does not alter the sensitivity of the muscle to caffeine. On the basis of these observations it has been suggested that veratrum alkaloids sensitize the muscle membrane essentially to depolarizing processes. 2. Cevadine, 0.01 mM, fails to depolarize the muscle membrane but increases the depolarizing effect of 10 mM potassium. The depolarizing effect of a reduction of the concentration of chloride from 120 mM to 30 mM is also increased in cevadine pretreated muscle. Cevadine pretreatment increases the depolarizing effect of nicotine, too. 3. The above sensitizing effects are unanimously Na-dependent. Accordingly there is no mechanical response and increased depolarization in muscles equilibrated in sodium-free (choline) Ringer's solution before the cevadine treatment. 4. On the basis of the present data it is suggested that the membrane, when sensitized by veratrum alkaloids, can be triggered by different depolarizing processes and the depolarization increases as the result of increased Na permeability. The increased depolarization at the threshold level becomes sufficient for the automatic regenerative processes of the action potential to develop which activate the contractile elements. However, the mechanical response is a prolonged contraction rather than a contracture, its long period being the result of a very slow repolarization caused by the well-known inhibitory effect of veratrum alkaloids on Na inactivation.