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].