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1. Neurotransmitter release has a non-linear dependence upon the external Ca concentration, [Ca]o. This may be due to a 'co-operative' action of Ca in triggering release. The dependence of presynaptic Ca currents and post-synaptic currents (p.s.c.s) upon [Ca]o was examined at voltage-clamped 'giant' synapses of squid to determine whether this 'co-operativity' occurs during or after influx of Ca into the presynaptic terminal. 2. Presynaptic Ca current was proportional to [( Ca]o/(1 + [Ca]o/KD]n, where n, the order of the function, was roughly 1 and KD, the apparent dissociation constant for Ca, was approximately 80 mM. 3. P.s.c.s also could be described by the same function, but had an n of 3-4 and a lower KD. 4. These results suggest that the 'co-operative' action of Ca occurs at a step or steps beyond entry of Ca into the presynaptic terminal. 5. Synaptic transfer curves relating presynaptic Ca currents, elicited by depolarizations to different potentials, to resultant p.s.c.s were power functions whose exponent depended upon [Ca]o. Maximum exponents were as high as 4 at [Ca]o of 3 mM. The dependence of these curves upon [Ca]o helps to explain why previous determinations, which were performed at a variety of [Ca]o levels, yielded a variety of transfer curve exponent values. 6. Transfer curves generated from responses to constant presynaptic depolarizations, with Ca current varied by [Ca]o changes, also were power functions with exponents of approximately 4. Thus p.s.c.s were high-exponent power functions of Ca current regardless of whether Ca current was modified by changes in membrane potential or in [Ca]o.

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