The interaction of extracellular H+, Na+, Ca2+ and Sr2+ on the decay of miniature end-plate currents.

We suggested previously that increases in the extracellular [Ca2+] or [Mg2+] lengthen miniature end-plate currents (m.e.p.c.s.) because the divalent cations decrease the negative surface potential on the end-plate, and thereby increase the voltage drop within the membrane. The increased voltage drop would lengthen the open time of the end-plate channels. Increased extracellular [H+] is also known to lengthen m.e.p.c.s.15; perhaps also acting by changing the surface potential. There has been dispute about the observations and their interpretation. Reducing the [Na+]0 at pH = 7.4 from 120 to 12 mM decreased the half-time of m.e.p.c. decay by nearly a factor of two. When the same changes in [Na+]0 were performed at pH = 5.2, no change in m.e.p.c. decay was detected. This suggests that the H+ titrates the negative surface charges, so they no longer can be affected by [Na+]0. The data do not fit the hypothesis that lifetime is determined by the presence of permeant ions in the channel 4,16. At pH = 7.4 replacing the 2.5 mM CaCl2 by SrCl2 decreased the m.e.p.c. decay rate by 60%17. This effect is not seen at pH = 5.2. We suggest that at pH = 7.4, Sr2+ binds to fixed negative charges on the end-plate and thereby slows the decay. H+ titrates the fixed charges and decreases the Sr2+ effect. In low [Na+] saline, raising [Ca2+]0 shortened m.e.p.c. decay--an effect exactly opposite to that expected from the change in surface potential. Under these conditions, increasing the [Ca2+] decreases the m.e.p.c. decay rate by some other mechanism; this second effect of Ca2+ on m.e.p.c. decay may account for some of the different results reported.