Post-tetanic potentiation at an identified synapse in Aplysia is correlated with a Ca2+-activated K+ current in the presynaptic neuron: evidence for Ca2+ accumulation.

Abstract

We have examined the presynaptic changes underlying post-tetanic potentiation (PTP) in Aplysia by using voltage-clamp techniques combined with specific pharmacological blocking agents. The amplitude and time course of PTP parallel a slow outward clamp current that we have identified as a Ca2+_ activated K+ current. Because this current is proportional to intracellular Ca2+ concentration our findings provide evidence for the "residual Ca2+ hypothesis," according to which PTP is caused by the accumulation of intracellular Ca2+ after tetanus. To obtain further evidence for this mechanism we injected EGTA intracellularly and found that it decreased the duration of both PTP and the Ca2+-activated K+ current.Post-tetanic potentiation (PTP) is a well-described form of synaptic plasticity whereby high-frequency stimulation of a presynaptic pathway leads to an increase in the amount of transmitter released (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Previous studies have shown that Ca2" plays an important role in PTP and that the potentiation is not dependent on the shape ofthe presynaptic spike and is affected by agents that alter the intracellular buffering capability for Ca2". On the basis ofthese observations Katz and Miledi (9,10) and Rahamimoff(11,12) have proposed that facilitation and PTP may result from residual increases in intracellular Ca2" due to Ca2O entry during the tetanus and-perhaps additionally-due to its subsequent release from internal stores by Na+. In previous analyses, it has not been possible to test the "residual Ca2" hypothesis" directly because the presynaptic terminal could not be impaled for intracellular recording. In addition, these analyses have been compromised because tetanic stimulation also gives rise to membrane potential changes in the presynaptic terminals that may have secondary effects on release, masking the actual time course of the facilitated release process. Recently, neurons have been described in Aplysia in which presynaptic release sites are accessible to intracellular electrodes and can be studied under voltage-clamp conditions, in which secondary changes in membrane potential can be controlled (13-15). One of these neurons, the identified cholinergic cell L10, makes connections to follower cells that undergo PTP. We have therefore analyzed the presynaptic ionic mechanisms underlying PTP at these synapses and have tested the idea that Ca2' accumulation contributes to PTP.To examine Ca2' accumulation we have relied on measurement of the Ca2+-activated K+ current in the presynaptic cell L10. This outward current is activated by intracellular Ca2+, and there is good evidence that this current provides an index of the amount and time course ofincreases in intracellular Ca2+ concentration (16)(17)(18). We here describe that PTP is paralleled by an increase in the Ca2"-activated K+ current and thus provide evidence for an increase in intracellular Ca2" during PTP.To test this model further we next blocked the accumulation of Ca2" before and after PTP by injecting the cal...

Regulation of excitatory transmission at hippocampal synapses by calbindin D28k.

“…For example, studies in the squid giant synapse have demonstrated that BAPTA attenuates neurotransmitter release, while EGTA has no effect (19,20). At the same time, however, EGTA is effective in preventing PTP (21). It is thought that EGTA fails to affect transmitter release for the same reason that it is less effective than BAPTA in preventing Ca2+-dependent inactivation of Ca2+ channels-i.e., its time constant of Ca2+ binding is too slow.…”

A Molecular Description of Nerve Terminal Function

“…Recent experiments on the squid stellate ganglion synapse (112) show that an alteration of Ca 2+ current of sufficient amplitude to cause facilitation would have been readily detected. Experiments on Aplysia neuron L10 show a close correspondence between facilitation and internal calcium as measured by the activity of the Ca 2+ -dependent K + channel (122). The kinetics of disappearance of facilitation are thought to be regulated by the time course of Ca 2+ removal (126).…”

“…REGULATION OF THE CALCIUM CHANNEL-All types of short-term synaptic plasticity that have been investigated in detail involve modulation of Ca 2+ levels in the terminals, though the mechanisms differ (121,122). The amount of Ca 2+ -influx during an action potential is primarily regulated by the opening and closing of Na + and K + channels (e.g.…”

“…121). In addition internal Ca 2+ levels depend on steady state Ca 2+ currents (123), Ca 2+ accumulation from previous action potentials (122), and direct modification of Ca 2+ channel activity (124,125).…”

Neural Mechanisms of Fine-Grained Temporal Processing in Audition

“…These features have many parallels with another kind of short-term plasticity, called "paired-pulse facilitation" [73]. Paired-pulse facilitation is thought to be caused chiefly by the residual elevation of the intracellular calcium concentration ([Ca 2+ ] i ) in presynaptic terminals [73,74] (Figure 14D). …”