Showing papers by "Stephen J. Smith published in 1987"

Calcium action in synaptic transmitter release.

Abstract: In this review we are concerned with the mechanisms by which the electrical potential across the membrane of presynaptic nerve terminals regulates the release of neurotransmitter substances into the synaptic cleft . Ca ions play a central role in this process: Release occurs when a voltage-depen­ dent Ca channel in the presynaptic membrane opens, thus permitting an influx of Ca ions and diffusion of Ca in cytoplasm, followed by binding of Ca at some cytoplasmic site that triggers the exocytotic release of quanta of neurotransmitter. These concepts, introduced mainly by the work of Katz and associates (Katz 1 969), comprise the "Ca hypothesis" of trans­ mitter release, a hypothesis now widely accepted. Although the general role of Ca as a presynaptic messenger is well supported, many important specifics of its action remain to be resolved. We review progress with these details in three parts, corresponding to

Cyclic AMP induces changes in distribution and transport of organelles within growth cones of Aplysia bag cell neurons

Abstract: This report examines cAMP-induced regulation of directed organelle transport in bag cell neuron growth cones using video-enhanced differential interference contrast (DIC) microscopy (Allen et al., 1981; Inoue, 1981) and digital image analysis techniques. Under control conditions, organelle transport is evident in the central cytoplasmic regions of bag cell neuron growth cones, but not in lamellae. Motility of lamellae takes the form of slow (less than 0.01 micron/sec) extension of margins and ruffling motions that propagate as waves (velocity, approximately 0.07 micron/sec) in a retrograde direction. Application of forskolin and a phosphodiesterase (PDE) inhibitor at concentrations known to induce changes in bag cell protein phosphorylation resulted in (1) rapid extension of directed organelle transport into lamellae, and (2) inhibition of the retrograde ruffling waves. These changes effected transformation of lamellae into neurite endings packed with microtubules and organelles, a large proportion of which appeared to be neurosecretory granules. The effects were reversible, dose-dependent, potentiated by a variety of PDE inhibitors, and mimicked by 6-N-butyl-8-benzyl-thio-cAMP (BT-cAMP). Though forskolin may normally promote depolarization and Ca entry, these changes in growth cone structure are not secondary to influx of external Ca, as they persist in Ca-free/EGTA solutions; furthermore, they do not resemble the effects of depolarization induced by perfusion with elevated K solutions. The cAMP-induced changes in growth cone morphology that we report here suggest a possible role for protein phosphorylation in promoting growth cone differentiation and structural changes accompanying secretion.

Slow membrane currents in bursting pace-maker neurones of Tritonia.

Abstract: 1. Membrane ionic currents in bursting pace-maker neurones of the marine mollusc Tritonia were studied in voltage-clamp experiments with emphasis on slow tail current relaxations after depolarizing pulses. 2. The slow tail current undergoes a complex transition from an initially inward current to an initially outward current as the duration of the depolarizing pulse is lengthened. It was found that the slow tail current is the sum of two separate and independent ionic currents. Methods were devised to study each current in isolation. 3. A slow inward tail current, termed IB, is activated by depolarization and decays exponentially on return to -55 mV with a time constant of 2-4 s. The voltage dependence and kinetics of IB activation were measured. Current amplitude is sensitive to removal of both Na+ and Ca2+ from the bathing medium but the current is not blocked by either tetrodotoxin (TTX) or replacement of Ca2+ by Co+. The amplitude of the current is independent of the external K+ concentration. 4. A slow outward tail current, termed IC, is also activated by depolarization. It is shown to be a K+ current whose activation results from an increase in the cytoplasmic Ca2+ concentration during depolarization. The decay of IC on repolarization requires more than 30 s to reach completion. 5. The slow rates of relaxation of IB and IC tail currents suggest that they are important determinants of the slow membrane potential variations characteristic of burst firing. IB activates more rapidly than IC during depolarization and is thought to be important for maintaining the depolarized phase of the burst cycle and for producing the depolarizing after-potential after each spike. IC activates more slowly but reaches greater amplitudes. It is thought to be important for adaptation in spike frequency during the burst, for burst termination, and for determining the duration of the interval between bursts.