A voltage-clamp study of the permeability change induced by quanta of transmitter at the mouse end-plate.

1. Miniature end-plate currents (m.e.p.c.s) were recorded from mouse diaphragm using a point voltage-clamp. The relation between m.e.p.c. amplitude and membrane potential was determined in bathing solutions of varied composition. 2. In solution containing normal sodium the relation between m.e.p.c. height and membrane potential (Im.e.p.c./Vm relation) was always linear, at least in the range +30 to -100 mV; the reversal potential (Vr) at which Im.e.p.c. was zero was close to 0. The slope of the Im.e.p.c./Vm line varied little between junctions (coefficient of variation about 20%) and was about 50 nS, or 1nA per 20 mV. The Im.e.p.c./Vm relation was not altered by withdrawal of Ca2+, addition of ethanol, or substitution of NO-3 or SO2-(4) for Cl-. 3. Alteration of K+ concentration in the bathing medium, in the range 10 to 1 mM, had no apparent effect on the Im.e.p.c./Vm relation. 4. Reduction of Na+ concentration, with isosmotic substitution of sucrose, caused rapid alteration of the Im.e.p.c./Vm relation, which became rectifying, with a slope at negative Vm less than at positive Vm. Vr was shifted in the negative direction. Quantitatively these changes were close to those predicted by the Goldman-Hodgkin-Katz formulation for permeation of monovalent ions through a membrane with constant field. 5. In solution with low Na+ (2 mM) and partial substitution of K+ for Na+, the Im.e.p.c./Vm relation was indistinguishable from that in solutions with Na" as the predominant extracellular cation. With complete substitution of K+ for Na+ the Im.e.p.c./Vm relation was a little less steep (at negative Vm) than in Na+ solution and Vr was shifted slightly in the negative direction. 6. With substitution of NH+4 for Na+, the Im.e.p.c./Vm relation was little changed (about 10% steeper at negative Vm). With substitution of Li+ for Na+, the Im.e.p.c./Vm relation remained linear, but was made less steep, at positive as well as negative Vm, and Vr was shifted slightly in the positive direction. 7. These results indicate that the permeability change associated with generation of the m.e.p.c. (i.e., evoked by a quantum of transmitter) corresponds to the opening of a single species of membrane channel that allows the free movement of K+, Na+, NH+4, AND Li+ ions along their electrochemical gradients. The channel discriminates little between these ions. The apparent order of permeability is Li+ greater than NH+4 greater than Na+ greater than or equal to K+. The apparent permeability per channel corresponds to that expected for channels of about 6.4 A diameter, 100 A length, and ionic mobility the same as in dilute solution.