Tetraethylammonium-induced contractions of frog's skeletal muscle. 3. Mechanism of action by calcium release.

Abstract

The effects of changes in the extracellular calcium concentration on the muscle 'twitching' response induced by tetraethylammonium of the frog's sartorius muscle were investigated. Decreasing the calcium concentration of a solution bathing the muscle increased the sensitivity of the muscle to TEA stimulation. However, with a sufficient calcium reduction (to 0.108 mM in most preparations) the muscles became completely insensitive to TEA stimulation. In contrast, calcium reduction resulted only in an increased muscle sensitivity to carbachol stimulation. Increasing the calcium concentration greatly decreased TEA sensitivity, and at 2.16 mM calcium a TEA-induced muscle 'twitching' response no longer could be produced. At this calcium concentration carbachol sensitivity was reduced but not eliminated and neuromuscular transmission was essentially unmodified. In studies with the toe muscle, it was found that TEA could restore the potassium-induced contracture that had been eliminated by soaking the muscle in a calcium-free solution. This effect of TEA was dependent upon the presence of a store of bound calcium in the muscle. These results are consistent with the hypothesis that TEA acts by releasing calcium from binding sites on the nerve endings, leading to an increased excitability and instability of these structures and resulting in the muscle twitching response. Other effects of TEA similar to those of increases in calcium are due to an increased level of ionized calcium at nerve and muscle membranes which also results from the release by TEA of calcium from membrane sites.