The interaction of presynaptic polarization with calcium and magnesium in modifying spontaneous transmitter release from mammalian motor nerve terminals.

1. The relationship between motor terminal polarization and miniature end-plate potential (m.e.p.p.) frequency was examined in the presence of various Ca, Mg and K concentrations ([Ca], [Mg] and [K]) and also at modified bathing osmolarity levels. The polarization changes were obtained with ;electrotonic' and ;focal' polarizing currents and with rapid changes in bathing [K].2. M.e.p.p. frequency increased exponentially with electrotonic depolarizing currents, but failed to decrease similarly with hyperpolarizing currents. An increase in bathing [K] to 15 mM increased the sensitivity of the terminals to presynaptic hyperpolarization.3. The slope, on semilogarithmic coordinates, of the function relating m.e.p.p. frequency to electrotonic polarizing currents (the release-current function) was unchanged when bathing [Ca] was raised from 2 to 8 mM. When [Ca] was reduced to 0.5 mM the slope of this function was reduced initially but eventually approached the same slope as in control [Ca]. A similar effect was also found in the presence of 15 mM-KCl.4. The relationship between m.e.p.p. frequency and log [K], at various [Ca], resembled the relationships between m.e.p.p. frequency and presynaptic polarizing currents.5. An increase in bathing [Mg] or osmolarity had a similar effect to a reduction of [Ca].6. Tetrodotoxin (TTX) at a concentration of 10(-6) g/ml. was found to reduce m.e.p.p. frequency, at various [K], by a constant fraction of about 30%.7. In some of the junctions ;anodic break-down' was observed. An examination of this phenomenon with focal polarizing currents disclosed an unusual type of ;anodic break-down', with rapid ;on' and ;off' responses. This phenomenon may indicate that release depends on the influx of positively charged particles into the nerve terminals.8. It is concluded that nerve terminal depolarization accelerates exponentially the activity of a membrane component bearing three Ca molecules, the rate of acceleration being independent of bathing [Ca].