Mechanisms of hexamethonium-induced tetanic fade in the isolated rat muscle.

The action of hexamethonium on neuromuscular transmission was investigated on the rat extensor digitorum longus muscle in vitro. Hexamethonium (5 x 10(-4) M) induced a complete fade of the tetanic contraction while leaving the twitch unaffected. At the same concentration, hexamethonium induced a significant decrease in the amplitude of the endplate potentials evoked at 50 and 100 Hz. Additionally, hexamethonium (5 x 10(-4) M) significantly increased the tetanic rundown of the endplate potential trains evoked at 100 Hz. The former effect was mainly the result of a frequency-independent decrease in the quantal size of the endplate potentials. This decrease seemed to be due to a postsynaptic blocking action of hexamethonium. The increase in tetanic rundown was due to a presynaptic action of hexamethonium. Such an action led to a frequency-dependent decrease in the quantal release of transmitter during repetitive stimulation of the motor nerve. It is concluded that both pre- and postsynaptic actions are necessary for hexamethonium to induce tetanic fade without affecting the twitch; and that, if it is accepted that the presynaptic action of hexamethonium is exerted on presynaptic receptors, these are not of the ganglionic type since the presynaptic effect of hexamethonium was less pronounced than the postsynaptic one.