THE ACTION OF TETRAETHYL‐AMMONIUM CHLORIDE ON THE RESPONSE OF THE RAT ANOCOCCYGEUS MUSCLE TO MOTOR AND INHIBITORY NERVE STIMULATION AND TO SOME DRUGS

Abstract

1 Tetraethylammonium chloride (TEA) 0.125 mm to 20 mm potentiates the response of the anococcygeus muscle to field stimulation of the motor adrenergic nerves without affecting the response to noradrenaline suggesting a pre-synaptic origin of potentiation. The potentiation is greatest at low, submaximal, frequencies (2 Hz) of stimulation and only slight at the higher frequency of 20 Hz. This difference is due to the restraint imposed on the demonstration of potentiation by maximal or near maximal motor responses since reduction of the mechanical response at 20 Hz by either phentolamine (post-synaptic block) or guanethidine (pre-synaptic block) resulted in a great increase in potentiation of the response at this frequency. 2 TEA in concentrations up to 1 mm similarly potentites the response to inhibitory nerve stimulation and again the greatest effect is at low frequencies. Higher concentrations (5–20 mm) progressively depress the inhibitory response. It is suggested that TEA may specifically antagonize the post-synaptic action of the inhibitory transmitter and that at higher concentrations of TEA this effect dominates the pre-synaptic action in increasing transmitter release. 3 TEA has no effect on the motor response to tyramine. 4 TEA (5–20 mm) causes a maintained rise in muscle tone. Part of this is abolished by phentolamine but part is resistant. A similar muscle stimulant action of TEA is observed in muscles from rats previously treated with 6-hydroxydopamine in which indirect sympathomimetic drugs and field stimulation could no longer produce a motor response. These results suggest that part of the motor effect of TEA is due to an increased spontaneous release of noradrenaline and part to a direct action on the muscle. 5 TEA 0.125 mm to 20 mm antagonize the stimulant action of carbachol. Dose-response curves show a parallel shift to the right with no change in the maximum response suggesting a competitive atropine-like action. Such an effect has previously been reported in amphibian tissue but not so far as we can determine in mammalian preparations. 6 The possible mode of action of TEA is discussed.