Ca channel inactivation by intracellular Ca injection into Helix neurones

Standen, N B

doi:10.1038/293158a0

Cited by 77 publications

(25 citation statements)

References 17 publications

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“…Although this observation may argue against a Ca2+-dependent inactivation, it could also indicate that the slow inactivation of Ca2+ entry which occurs in Torpedo synaptosomes may not result from intracellular Ca2+ accumulation as has been proposed for fast-inactivating Ca2+ channels (Eckert & Tillotson, 1981;Standen, 1981), but rather from an effect of Ca2+ during their passage through the channel.…”

Section: Release Of Ach Induced By Other Depolarizing Agentsmentioning

confidence: 77%

“…Ca2+-dependent inactivation of voltage-dependent Ca2+ influx is already well documented in Paramecium (Brehm & Eckert, 1978); mollusc neurones (Kostyuk & Krishtal, 1977;Akaike, Lee & Brown, 1978; Tillotson, 1979;Standen, 1981), insect muscles (Ashcroft & Standfield, 1982) and heart cells (Brown, Kimura & Noble, 1981;Mentrard, Vassort & Fischmeister, 1984); the time course of this inactivation is rapid and lasts generally less than 1 s. However, inactivation of Ca2+ currents on this time scale was not found at the squid giant synapse (Katz & Miledi, 1971;Llinas, Sugimori & Simon, 1982) or in chromaffin cells (Fenwick, Marty & Neher, 1982), i.e. in the case of Ca2+ channels involved in excitation-secretion coupling.…”

Section: Release Of Ach Induced By Other Depolarizing Agentsmentioning

confidence: 99%

“…This effect has been attributed to the strong depolarizing properties of this ionophore which abolished the membrane potential of Torpedo synaptosomes (Meunier, 1984 (Eckert & Tillotson, 1981;Standen, 1981). This possibility was tested in Torpedo synaptosomes using a low dose of Glycera venom (equivalent to 0-23 venom gland/ml) which was sufficient to promote an entry INACTIVATION OF ACh RELEASE As the same pattern of release was observed whatever the size of ACh release, it is very unlikely that depletion of the transmitter store was involved.…”

Section: Release Of Ach Induced By Other Depolarizing Agentsmentioning

confidence: 99%

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Inactivation of acetylcholine release from Torpedo synaptosomes in response to prolonged depolarizations.

Birman¹,

Meunier²

1985

The Journal of Physiology

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SUMMARY1. The release ofacetylcholine (ACh) from purely cholinergic Torpedo synaptosomes was monitored continuously using a chemiluminescent assay .2. Upon prolonged K+ depolarization in the presence of Ca2+, the release of ACh was transient and returned to a steady low level in about 3 min. Addition of the Ca2+ ionophore A23187 triggered the release again, suggesting that neither depletion of the transmitter store nor an inhibition of the release mechanism itself were involved in this phasic response, but rather an inactivation of the Ca2+ entry.3. The release response evoked by adding Ca2+ back after exposure of the synaptosomes to high K+ (70 mM) and low Ca2+ (0 57 mM) solution inactivates as a function of the duration of the pre-depolarization with a two-component time course with rapid (T = 5-5 s) and slow phases ('r = 143 s).4. This response to Ca2+ addition was more strikingly reduced as the level of depolarization during pre-treatment was increased.5. The inactivation was found to be dose dependent with respect to the amount of Ca2+ present during the pre-depolarization period (conditioning Ca2+). Moreover, the presence of EGTA during pre-treatment with high-K+ solutions increased the response to applied Ca2+. These observations suggest that Ca2+ entry itself was responsible for this inactivation. 6. No inactivation was found when ACh release was induced by the depolarizing agent Gramicidin D, except when external Na+ was replaced by Li+. This result indicates that part of the Ca2+ influx promoted by Gramicidin D depends on a Na+ entry, and may be mediated by the Na-Ca exchange mechanism.

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Section: Release Of Ach Induced By Other Depolarizing Agentsmentioning

confidence: 77%

Section: Release Of Ach Induced By Other Depolarizing Agentsmentioning

confidence: 99%

Section: Release Of Ach Induced By Other Depolarizing Agentsmentioning

confidence: 99%

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Inactivation of acetylcholine release from Torpedo synaptosomes in response to prolonged depolarizations.

Birman¹,

Meunier²

1985

The Journal of Physiology

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“…Calcium influx through voltage-sensitive channels is an integral part of stimulus-secretion coupling in the neural lobe, and the facilitation of hormone release that accompanies increasing stimulus duration between 5 and 20 s may reflect the persistence of elevated calcium levels at release sites (Nordmann, 1976). However, similar calcium channels in other systems are known to be subject to a delayed inactivation, which may itself be calcium dependent (Eckert & Tillotson, 1981;Standen, 1981). Such inactivation, with a subsequent drop in calcium influx could result in the dramatic decline of vasopressin release beyond the first 18-36 s of a period of electrical stimulation.…”

Section: Discussionmentioning

confidence: 99%

Reversible fatigue of stimulus‐secretion coupling in the rat neurohypophysis.

Bicknell¹,

Da²,

Chapman³

et al. 1984

The Journal of Physiology

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SUMMARY1. Single rat neurointermediate lobes were impaled on a stimulating electrode and continuously perifused with oxygenated medium. The secretion of oxytocin and vasopressin into the medium was measured by specific radio-immunoassays.2. The temporal profile of vasopressin release during a 20 min period of 13 Hz stimulation was compared with that of oxytocin. The results indicate that although the rate of secretion of both oxytocin and vasopressin declines over 20 min, the extent and time course of this fatigue is different for the two hormones. This difference could not be accounted for by differences in the rate of diffusion of released hormone from the tissue which was similar to the rate of wash-out of [14C]sucrose from the extracellular space in pre-labelled glands.3. In separate experiments glands were exposed to a prolonged period (60-70 min) of 13 Hz stimulation interrupted by brief silent periods (30 s-2 min duration). Some recovery from the fatigue of vasopressin secretion was evident after even the shortest of these silent periods.4. In further experiments glands were stimulated electrically for 18, 36, 54 and 72 s at 13 Hz: the order of presentation of the periods of stimulation was randomized between experiments. The vasopressin release rate declined markedly and progressively between 18 and 72 s. In contrast, the oxytocin release rate was relatively uniform throughout 72 s of stimulation. Thus vasopressin secretion is subject to a relatively rapid and dramatic fatigue.5. The results support the hypothesis that the phasic discharge patterns characteristic of vasopressin secreting neurones optimize the efficiency of vasopressin release from the nerve terminals in the neurohypophysis by avoiding the fatigue of stimulus-secretion coupling that accompanies continual stimulation.

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“…Under physiological conditions, repetitive stimulation of the synapse gives a linear increase with time in intraterminal Ca 2+ (111,112). In many cells, however, a slow inactivation of Ca 2+ channels is seen (128,129). Half times of inactivation are typically about 100 msec, but range from 5 to 1000 msec (106).…”

Section: Biochemical Nature Of the Ca 2+ Channel-progress In Camentioning

confidence: 99%

A Molecular Description of Nerve Terminal Function

Reichardt¹,

Kelly²

1983

Annu. Rev. Biochem.

226

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The nerve terminal is a specialized region of a neuron, separated from the neuronal soma by an axon that can be exceedingly long, whose function is to release neurotransmitter when stimulated by an electrical signal carried by the axon. In this review, we describe the enzymes, channels, and other proteins presently thought to be important in nerve terminal function. Recent progress in the area has been so dramatic that it is becoming possible to relate simple changes in behavior to modifications of defined proteins in particular nerve terminals.Neurotransmitters are stored in synaptic vesicles and are released by fusion of these vesicles to the plasma membrane. Vesicle fusion is triggered by Ca 2+ -influx through specific Ca 2+ channels that open in response to depolarization of the plasma membrane and is terminated by the disappearance of Ca 2+ from the vicinities of the active zones. The voltage signal that opens the Ca 2+ gates is not constant, but also subject to regulation. The key elements are the Na + and K + channels in the nerve terminal. These channels are localized to distinct regions of many neurons and different neurons have different quantities of the different channel types. The voltage sensitive Na + channel is responsible for depolarizing the membrane. This channel has recently been purified and reconstituted in artificial membranes, so many of its properties are known. K + channels are responsible for repolarizing the membrane. Several K + channels have been identified: some activated by voltage, some by intracellular Ca 2+ and others by neurotransmitters. The properties of several of these have recently been shown to be altered by cAMP-dependent protein kinases, resulting in long-term changes in neuronal activity and the efficiency of synaptic transmission. The voltage-dependent Ca 2+ channels can also be modified by cAMP-dependent protein kinases. Many of the neurotransmitters and hormones that modulate the efficiency of transmitter release apparently do so by modifying the Ca 2+ channels. Much of the recent progress in molecular studies on the K + and Ca 2+ channels has been made possible by a dramatic new technique called "patch clamping" that permits individual ion channels to be examined on the tip of a microelectrode. In many ways this technology circumvents the need for biochemical isolation and reconstitution.Maintenance of the Na + and K + concentrations in neurons requires the classical Na, + K + -ATPase that is found in all cell types. Recent experiments suggest that a novel form of this enzyme exists in neural tissues. This pump appears to be localized to anatomically and functionally distinct regions of many neurons. To restore the cytoplasmic Ca 2+ concentrations to original levels, the nerve terminal has an array of Ca 2+ removal systems including a Na + :Ca 2+ antiporter in the plasma membrane, a Ca 2+ porter in the mitochondrial inner membrane and several distinct ATP-dependent Ca 2+ uptake systems in the plasma membrane, smooth endoplasmic reticulum, and synaptic vesicles.The...

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Ca channel inactivation by intracellular Ca injection into Helix neurones

Cited by 77 publications

References 17 publications

Inactivation of acetylcholine release from Torpedo synaptosomes in response to prolonged depolarizations.

Inactivation of acetylcholine release from Torpedo synaptosomes in response to prolonged depolarizations.

Reversible fatigue of stimulus‐secretion coupling in the rat neurohypophysis.

A Molecular Description of Nerve Terminal Function

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