Abstract

The effect of quinacrine was studied on neuromuscular transmission in frog sartorius and rat soleus muscles and on the binding of ligands to the electric organ of Torpedo ocellata. Quinacrine (30-200 µM) blocked neuromuscular transmission in both muscles, and inhibited the carbamylcholine-induced membrane depolarization at the endplate. The most pronounced effect of quinacrine was on the acetylcholine (ACh)-receptor mediated postsynaptic conductance. It reduced the endplate current (EPC) peak amplitude, without marked departure from linearity of the current voltage relationship, and it shortened the EPC rise time. The rate of decay of the EPC was also altered by quinacrine, becoming less voltage-dependent at concentrations of about 5 µM and completely voltage-independent at drug concentrations of 30-100 µM. Biochemical studies on membranes from electric organ of the electric ray Torpedo ocellata revealed that quinacrine inhibited the binding of [³H]ACh and [³H]H₁₂-HTX to the membrane-bound ACh-receptor and its ionic channel, respectively. The inhibition constant (K_i) values were 7.4 µM and 14 µM, respectively. It is suggested that the mode of action of quinacrine on neuromuscular transmission is complex and reflects interaction with both the ACh-receptor and its ionic channel.