A reappraisal of the evidence for a direct action of tetraethylammonium on the chick biventer cervicis muscle equilibrated with lidocaine.

Contractures of the chick biventer cervicis muscle were recorded in vitro in response to exogenous acetylcholine (ACh) and to tetraethylammonium (TEA) and concentration response curves (CRC) produced for these drugs. In BVC muscles equilibrated with lidocaine (1.07 mM), physostigmine (3.63 microM) blocked TEA induced contractures in a reversible non-competitive manner. It had a similar action on ACh induced contractures. Lidocaine (1.07 mM) had no action on the ACh CRC except that it reduced the response to the highest concentration of ACh tested. The data of this and of previous experiments was analyzed and a theory proposed to account for TEA contractures. It suggested that background extravesicular ACh release results in the passage of K+ into the transverse tubular system (TT). In the presence of TEA blocking the K+ channels accumulation of K+ in the TT no longer occurs. Na+/K+ exchange is depressed in favour of Na+/Ca+ exchange and the resulting rise in intracellular Ca2+ acting on the sarcoplasmic reticulum leads to contraction. Lidocaine potentiates the contraction by blocking Ca2+ uptake into the sarcoplasmic reticulum.