User:Sabelson/sandbox

Mechanisms
The amount of Calcium influx after membrane depolarization affects the probability of neurotransmitter release. As shown by Katz and Miledi (1967) after performing experiments on the neuromuscular junction of a frog, a second nerve impulse elicits a greater chance of neurotransmitter release. To explain this phenomenon, Katz and Miledi (1967) proposed the residual Calcium hypothesis and attribute the increase in neurotransmitter release to residual or accumulated Calcium, "active calcium," within the axon membrane that remains attached to the membrane's inner surface. They manipulated Calcium concentration to determine whether or not residual calcium during the second impulse in fact heightened neurotransmitter release. During the first nerve impulse, Calcium concentration was either significantly below or nearing that of the second impulse. When Calcium concentration was approaching that of the second impulse, facilitation was increased. In this first experiment, stimuli were presented in intervals of 100 msec between the first and second stimuli. Absolute refractory was reached when intervals were about 10msec apart. To examine facilitation during shorter intervals, Katz and Miledi (1967) directly applied brief depolarizing stimuli to nerve endings. When increasing the depolarizing stimulus from 1-2 msec, neurotransmitter release greatly increased due to accumulation of active calcium. Therefore, the degree of facilitation depends on the amount of active calcium, which is determined by the reduction in calcium conductance over time as well as the amount of calcium removed from axon terminals after the first stimulus. Facilitation is greatest when the impulses are closest together because calcium conductance does not return to baseline prior to the second stimulus. Therefore, both calcium conductance and accumulated calcium would be greater for the second impulse. The residual calcium hypothesis specifically accounts for short-term facilitation (STF), similar to post-tetanic facilitation (PTF) and may result from the binding of residual ca 2+ to sensors within the membrane different from those mediating ca2+ exocytosis ==footnote 2==