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M R Bennett

Publications and source records attributed to M R Bennett.

At least 163 records · Page 9Linked to original sources
PubMed1994

c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines.

We have investigated the mechanism by which deregulated expression of c-Myc induces death by apoptosis in serum-deprived fibroblasts. We demonstrate that Myc-induced apoptosis in low serum is inhibited by a restricted group of cytokines, principally the insulin-like growth factors and PDGF. Cytokine-mediated protection from apoptosis is not linked to the cytokines' abilities to promote growth. Protection from apoptosis is evident in the post-commitment (mitogen-independent) S/G2/M phases of the cell cycle and also in cells that are profoundly blocked in cell cycle progression by drugs. Moreover, IGF-I inhibition of apoptosis occurs in the absence of protein synthesis, and so does not require immediate early gene expression. We conclude that c-Myc-induced apoptosis does not result from a conflict of growth signals but appears to be a normal physiological aspect of c-Myc function whose execution is regulated by the availability of survival factors. We discuss the possible implications of these findings for models of mammalian cell growth in vivo.

Animals↗
PubMed1994

Retinal ganglion cell survival in vitro maintained by a chondroitin sulfate proteoglycan from the superior colliculus carrying the HNK-1 epitope.

We recently reported evidence implicating a superior colliculus-derived chondroitin sulfate proteoglycan (SCCP) in the trophic support of cultured retinal ganglion cells (Schulz et al., 1990). In the present work we show preparations of the SCCP to be reactive with an antibody (CS-56) to chondroitin sulfate types A and C and with the HNK-1 antibody. Reaction with the HNK-1 antibody allowed us partially to purify the native proteoglycan by immunoaffinity chromatography. HNK-1 reactive material was further processed by a combination of molecular sieve chromatography in the presence of 4M guanidine HCL followed by anion exchange chromatography to yield a product that migrated electrophoretically as a single band in polyacrylamide gel with an apparent molecular weight of not less than 400 k. The SCCP, when added to a fully defined culture medium, maintained the survival of the vast majority (80%) of the ganglion cells over a 16 hr culture period with 86% of these cells showing a profusion of processes; few ganglion cells (10%) survived in the absence of the proteoglycan. Electrophoretic analysis of nonreduced preparations of the molecule did not reveal any low molecular weight silver stained components that may have remained associated with the molecule after guanidine HCL treatment. However, two bands corresponding to molecular weights of around 60 and 80 k were reproducibly observed on polyacrylamide gels following electrophoresis of the molecule in the presence of beta-mercaptoethanol. Our findings provide further evidence suggesting a role for a chondroitin sulfate proteoglycan carrying the HNK-1 epitope in the trophic support of central neurones.

Animals↗
PubMed1994

Dynamics of the CA3 pyramidal neuron autoassociative memory network in the hippocampus.

A theory for the dynamics of sparse associative memory has been applied to the CA3 pyramidal recurrent network in the hippocampus. The CA3 region is modelled as a network of pyramidal neurons randomly connected through their recurrent collaterals. Both the elliptical spread of the axonal systems and the exponential decrease in connectivity with distance are taken into account in estimating the connection probabilities. Pyramidal neurons also receive connections from inhibitory interneurons which occur in large numbers throughout the network; these in turn receive inputs from other inhibitory interneurons and from pyramidal neurons. These inhibitory neurons are modelled as rapidly acting linear devices which produce outputs proportional to their inputs; they perform an important regulatory function in the setting of the membrane potentials of the pyramidal neurons. The probability of a neuron firing in a stored memory, which determines the average number of neurons active when a memory is recalled, can be set at will. Memories are stored at the recurrent collateral synapses using a two-valued Hebbian. Allowance is made in the theory both for the spatial correlations between the learned strengths of the recurrent collateral synapses and temporal correlations between the state of the network and these synaptic strengths. The recall of a memory begins with the firing of a set of CA3 pyramidal neurons that overlap with the memory to be recalled as well as the firing of a set of pyramidal neurons not in the memory to be recalled; the firing of both sets of neurons is probably induced by synapses formed on CA3 neurons by perforant pathway axons. The firing of different sets of pyramidal neurons then evolves by discrete synchronous steps. The CA3 recurrent network is shown to retrieve memories under specific conditions of the setting of the membrane potential of the pyramidal neurons by inhibitory interneurons. The adjustable parameters in the theory have been assigned values in accord with the known physiology of the CA3 region. Certain levels of overlap between the input and the memory to be retrieved must also be satisfied for almost complete retrieval. The number of memories which can be stored and retrieved without degradation is primarily a function of the number of active neurons when a memory is recalled and the degree of connectivity in the network. The inhomogeneity in the connectivity of the pyramidal cells improves both capacity and overlap of the final state with the memory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Calcium concentration changes in the calyciform nerve terminal of the avian ciliary ganglion after tetanic stimulation.

A study has been made of the changes in calcium concentration in the calyciform nerve terminal ([Ca]c) and in the neurone soma ([Ca]s) of avian ciliary ganglion cells following tetanic stimulation of the nerve terminal. Dissociated ciliary neurones were loaded with the calcium indicator Fura-2 and digital imaging techniques used to determine the spatial and temporal distribution of calcium in the cells during post-tetanic potentiation (PTP) and long-term potentiation (LTP). Stimulation of the calyciform terminal with an extracellular electrode at 10 Hz for 2 s increased both [Ca]s and [Ca]s over 3-fold, with the [Ca] increasing for each impulse in the facilitatory train. The increase in [Ca]s could be prevented by allowing the terminal to degenerate in culture before stimulation. Stimulation of the calyciform terminal with a long tetanus of 30 Hz for 20 s gave an over 4-fold increase in both [Ca]c and [Ca]s by the end of the train. Analysis of the decline in [Ca]c after the train showed that it disappeared from the calyx along a double exponential time course with time constants of about 1 min and 50 min, respectively. These times are similar to those of PTP and LTP in the ganglia, and are almost independent of the extracellular calcium level. In order to determine whether the influx of calcium ions during a tetanus was through N-type calcium channels, these were blocked with adenosine (100 microM). Adenosine blocked the increase in both [Ca]s and [Ca]c that normally accompanies a tetanus. Thapsigargin (200 nM) did not affect [Ca]c or [Ca]s, but blocked transient increases in [Ca] caused by caffeine (10 mM) in both 3 mM and Ca2+ free bath solutions. These results are discussed in relation to the role of intracellular calcium in initiating LTP after a tetanus to the nerve terminals.

Adenosine↗
PubMed1994

Nitric oxide release and long term potentiation at synapses in autonomic ganglia.

1. Long-term potentiation (LTP) of synaptic transmission in autonomic ganglia is reviewed, together with the possible role of nitric oxide (NO) in this process. 2. Calcium levels in preganglionic nerve terminals are elevated during at least the induction phase of LTP following a tetanus as well as during LTP induced by transmitter substances acting on the nerve terminals. Of the large number of calcium-dependent processes in the nerve terminal that might affect transmitter release, only calcium-calmodulin has been shown to be important in both the induction and maintenance of LTP. 3. The possibility that there is a decrease in the open time of nerve-terminal potassium channels following a tetanus, leading to an increase in duration of the terminal action potential and hence an increase in calcium influx and transmitter release is considered. There is little evidence for such an effect as yet for preganglionic nerve terminals. 4. Phosphorylation of potassium channels by cAMP-dependent protein kinase can lead to their inactivation with consequent action potential broadening in some systems. Exogenous cAMP enhances synaptic efficacy at preganglionic nerve terminals. Whether this occurs through an inactivation of potassium channels is not known. 5. Nitric oxide (NO) synthase is present in both sympathetic ganglia and the ciliary ganglia. NO increases synaptic efficacy in both ganglia. In at least the case of ciliary ganglion this is due to elevation of quantal secretion. 6. NO can in some conditions increase the terminal action potential duration in ciliary ganglia, probably through decrease in the Ic potassium current. There is evidence that this happens through cGMP modulating cAMP phosphodiesterases, thereby affecting cAMP phosphorylation of the Ic channel. 7. Blocking NO synthase markedly decreases LTP following a tetanus in the ciliary ganglion. The possibility is considered that NO is released from the terminal during a tetanus and through altering cAMP phosphorylation of Ic enhances transmitter release.

Animals↗
PubMed1994

Effect of nitric oxide synthase inhibition on long-term potentiation at associational-commissural and mossy fibre synapses on CA3 pyramidal neurones.

1. The sensitivity of long-term potentiation (LTP) to nitric oxide synthase (NOS) inhibition was determined for two synaptic input systems onto CA3 pyramidal neurones the LTP of which display differential sensitivity to N-methyl-D-aspartate (NMDA) receptor antagonists: the fimbrial input which activates the associational-commissural synapses on the distal apical dendrites and the mossy fibre input which synapses on the proximal apical dendrites of CA3 pyramidal neurones. 2. Following high-frequency stimulation (HFS) of the fimbrial input, average e.p.s.p. amplitude increased by 92.4 +/- 22.0% (mean +/- s.e.mean; n = 6 cells) when compared to the pre-HFS average. In the presence of 100 microM N omega-nitro-L-arginine methyl ester (L-NAME), the enhancement was reduced significantly to 32.2 +/- 11.6% (n = 5 cells; P < 0.05). In the presence of 300 microM L-NAME, the inhibition was more complete, with post-HFS e.p.s.p. amplitude increasing an average 6.2 +/- 9.3% (n = 7 cells, P < 0.05). 3. Following high frequency stimulation of the mossy fibre input, average e.p.s.p. amplitude increased by 57.9 +/- 13.0% (n = 6 cells) when compared to the pre-HFS average. The presence of 100 microM L-NAME had no significant effect on the enhancement, averaging 63.6 +/- 5.9% (n = 4 cells; P > 0.05). Similarly, increasing the concentration of L-NAME to 300 microM had no significant effect on the potentiation, with the post-HFS amplitude increasing by an average 55.6 +/- 9.5% (n = 5 cells, P > 0.05). 4. These results suggest that LTP at associational-commissural synapses (fimbrial input) is significantly depressed in the presence of the NOS inhibitor L-NAME, while mossy fibre LTP is unchanged.

Amino Acid Oxidoreductases↗
PubMed1994

Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis.

We have investigated the requirement for c-myc downregulation in the growth arrest of vascular smooth muscle cells (VSMCs). Rat VSMCs were infected with a retrovirus vector directing constitutive expression of either the complete human c-Myc protein (VSM-myc cells) or the c-Myc deletion mutant D106-143, which is inactive in cotransformation and autosuppression assays (VSM-D106-143 myc cells). Clones of transfected VSM-myc cells were isolated that constitutively expressed a range of levels of c-Myc protein from that observed in normal proliferating VSMCs to approximately seven times normal. The growth rates of these clones and their responses to growth inhibitors were then assessed. VSM-myc clones possessed a shorter mean intermitotic time than normal cells, which was inversely correlated (P < .05) with the level of c-Myc protein expressed. VSM-myc cells also expressed lower levels of alpha-smooth muscle actin mRNA and protein and exhibited an altered morphology. The proliferation of normal VSMCs and VSM-D106-143 myc cells was inhibited by serum reduction (0.5% fetal calf serum) and also by treatment with interferon-gamma (100 IU/mL), heparin (50 micrograms/mL), 8-bromo-cAMP (0.1 mmol/L), or 8-bromo-cGMP (0.1 mmol/L). In contrast, proliferation of VSM-myc cells was not inhibited by any of these agents, even if present at 10-fold higher concentrations. However, approximately 75% of VSM-myc cells expressing levels of c-Myc protein seen in normal proliferating VSMCs underwent apoptosis after 4 days of serum reduction or treatment with interferon-gamma. The results show that constitutive c-myc expression induces continuous cell proliferation, reduction in alpha-smooth muscle actin expression and apoptosis in VSMCs. We conclude that downregulation of c-myc is a prerequisite for growth arrest and subsequent survival of VSMCs. Conversely, deregulated c-myc expression may be important in the proliferation and death of VSMCs--characteristics of the pathogenesis of atherosclerosis.

Actins↗
PubMed1994

Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides.

Restenosis after angioplasty is due predominantly to accumulation of vascular smooth muscle cells (VSMCs). The resistance of restenosis to pharmacological treatment has prompted investigation of genes involved in VSMC proliferation. We have examined the effect on VSMC proliferation of blocking expression of the c-myc proto-oncogene with antisense oligodeoxynucleotides, both in vitro and in a rat carotid artery injury model of angioplasty restenosis. Antisense c-myc oligodeoxynucleotides reduced average cell levels of c-myc mRNA and protein by 50-55% and inhibited proliferation of VSMCs when mitogenically stimulated from quiescence or when proliferating logarithmically (IC50 = 10 micrograms/ml). Corresponding sense c-myc, two-base-pair mismatch antisense c-myc, antisense alpha-actin or glyceraldehyde phosphate dehydrogenase oligodeoxynucleotides did not suppress c-myc expression or inhibit VSMC proliferation. Antisense c-myc inhibition was relieved by overexpression of an exogenous c-myc gene. After balloon catheter injury, peak c-myc mRNA expression occurred at 2 h. Antisense c-myc applied in a pluronic gel to the arterial adventitia reduced peak c-myc expression by 75% and significantly reduced neointimal formation at 14 d, compared with sense c-myc and gel application alone. We conclude that c-myc expression is required for VSMC proliferation in vitro and in the vessel wall. C-myc is a therefore a potential target for adjunctive therapy to reduce angioplasty restenosis.

Animals↗
PubMed1993

Evidence that each nerve varicosity on the surface of the mouse vas deferens secretes ATP.

The secretion of ATP from visualised varicosities on the surface of the mouse vas deferens was determined. Small diameter microelectrodes (about 6 microns and 20 microns) were placed over a set of 2 to 5 varicosities visualised with DiOC2(5) in order to record excitatory junctional currents (e.j.c.s') arising from the evoked secretion of quanta. In high external calcium concentrations, [Ca2+]o, the amplitude-frequency distribution of e.j.c.s' was well described by binomial statistics in which binomial parameter n and the number of varicosities were approximately the same. Idazoxan (1 microM) had no effect on the e.j.c.s' or the binomial parameters p and n. Suramin (100 microM) blocked the e.j.c.s' as well as the spontaneous e.j.c.s' (s.e.j.c.s') in all cases, reducing n and p to zero. These results indicate that all varicosities secrete the transmitter blocked by suramin, presumably ATP.

Adenosine Triphosphate↗
PubMed1993

Extracellular current flow and potential during quantal transmission from varicosities in a smooth muscle syncytium.

A discrete model has been developed that describes the extracellular current that flows in a smooth muscle syncytium upon the secretion of a quantum of transmitter onto a smooth muscle cell in the syncytium. This allows a description to be given of the current (called the excitatory junctional current (EJC)) recorded by an electrode of given diameter placed on the surface of the muscle, during synaptic transmission from a varicosity situated anywhere in the muscle. The EJC is of maximum negative amplitude when the varicosity is at the surface of the muscle near the inside rim of the electrode and decreases as the varicosity moves to the centre of the electrode. It is of maximum positive amplitude when the varicosity is at the surface near the outside rim of the electrode and declines rapidly in amplitude as the varicosity is removed further from the outside rim. Smaller diameter electrodes give larger EJCs than larger diameter electrodes for most positions of the varicosity on the surface of the muscle. The EJC amplitude declines for varicosities beneath the electrode that are not on the surface of the muscle, but deep in the tissue. The rate of this decline is greater the smaller the diameter of the electrode. The time-course of the EJC is largely invariant under changes in the position of the varicosity with respect to the recording electrode. Changes in the polarity of the current flow during a single EJC can occur, however, if two varicosities secrete transmitter simultaneously, one inside the electrode and one outside, and the time-course of the currents due to the individual varicosities is either the same or slightly different. This theoretical work has been used to interpret a number of recent experimental studies of extracellular current flow during autonomic neuromuscular transmission.

Animals↗
PubMed1993

Effect of proteoglycan purified from rat superior colliculus on the survival of murine retinal ganglion cells.

Recently, Schulz and coworkers purified a chondroitin sulfate proteoglycan from the superior colliculus of the neonatal rat which promoted survival of neonatal rat retinal ganglion cells in vitro. The present work tests whether this factor supports the survival of axotomised retinal ganglion cells in vivo. To this effect, murine retinae 15 and 20 days after conception were explanted to the chorioallantoic membrane of live chicken embryos. The explants, which were left in the egg for 1, 2 or 7 days, differentiated and grew according to a normal timetable. Purified proteoglycan from neonatal rat superior colliculus was applied daily to one group of retinae while a control group received Ham's F-10 medium. Results indicated that application of proteoglycan resulted in the preferential survival of large cells in the ganglion cell layer, namely ganglion cells, for up to 7 days post-explantation. In addition, the proteoglycan had a significant short-term anti-traumatic effect on the ganglion cell layer of explants by causing a 72% decrease in the number of dead cells relative to controls 1 day post-explantation. It was concluded that the chondroitin sulfate proteoglycan purified from the superior colliculus of the neonatal rat promotes the survival of fetal and neonatal murine retinal ganglion cells in retinae explanted to the chorioallantoic membrane of the chick.

Animals↗
PubMed1993

Sympathetic innervation of the surface of the mouse vas deferens.

The distribution of axons and axon varicosities on the surface of the mouse vas deferens has been determined following fluorescence of these structures with 3,3-diethyloxardicarbocyanide (DiOC2 (5)) to locate varicosities and FAGLU to detect catecholamine containing nerves. Small bundles of fluorescent axons treated with DiOC2(5), were shown to give rise to single or very small bundles of 2 or 3 varicose axons that passed over the surface of the muscle bundles. Varicosities had the same average diameter of 0.9 microns, length of 1.1 micron and spacing apart of 4.6 microns whether identified following DiOC2(5) fluorescence or the FAGLU method for catecholamines and this was shown statistically to imply that they came from the same population of varicosities. Serial thin sections through small axon bundles and single axons, viewed with the electron microscope, confirmed the dimensions of varicosities along axons observed following DiOC2(5) staining or use of the FAGLU method.

Animals↗
PubMed1993

Probabilistic secretion of quanta from successive sets of visualized varicosities along single sympathetic nerve terminals.

Quantal secretion was recorded from adjacent sets of varicosities along the length of single sympathetic nerve terminals that had been visualized with the fluorescent dye, 3,3-diethyloxardicarbocyanine iodide (DiOC2(5)). Recordings were made with both small diameter microelectrodes (4-6 microns) placed over 1-3 varicosities and large diameter microelectrodes (20-50 microns) placed over 3-7 varicosities. The proportion of trials in which secretion occurred from sets of varicosities declined in general for the adjacent sets of varicosities along the length of single sympathetic nerve terminals. The amplitude-frequency distributions of excitatory junctional currents (EJCs) were in general predicted by Poisson statistics and occasionally by binomial statistics. The mean quantal content of the EJC in general declined over threefold along the length of single sympathetic nerve terminals for adjacent sets of varicosities.

Animals↗
PubMed1993

Conditions of oocyte storage and use of noninseminated as compared with inseminated, nonfertilized oocytes for the hemizona assay.

OBJECTIVES: To examine differences in sperm binding to the zona and recovery of oocytes from the storage vessel after oocyte preservation for the hemizona assay (HZA) by the method currently in predominant use, salt storage at 4 degrees C, as compared with a new method that should allow for indefinite preservation of zona receptors, dimethylsulphoxide (DMSO)/sucrose in liquid nitrogen (-196 degrees C). A second objective was to compare sperm binding to noninseminated zona as opposed to zona from inseminated, nonfertilized oocytes and to examine whether differences in binding potential were related to the patient's fertilization rate from the cycle in which the oocytes for the HZA originated. DESIGN: Binding and recovery were evaluated after 1, 2, 3, 6, 9, 12, and 17 to 25 months of storage. SETTING: In vitro fertilization and andrology laboratories at the University of Iowa Hospitals and Clinics; academic tertiary care center. RESULTS: Binding of sperm was significantly lower for nonfertilized oocytes stored > 12 months in salt at 4 degrees C than for those stored in liquid nitrogen. Binding was similar after storage for 1, 2, 3, 6, 9, and 12 months. Oocyte recovery was significantly lower after storage in salt for > 12 months as compared with storage in liquid nitrogen. Greater variability in sperm binding was observed between matching zona halves of nonfertilized as compared with noninseminated oocytes. Nonfertilized oocytes also bound fewer total sperm than noninseminated oocytes. The number of sperm bound to noninseminated oocytes was not related to the patient's fertilization rate from the cycle in which the oocytes originated. However, significantly fewer sperm bound to the zona of nonfertilized oocytes when the oocyte originated from a cycle in which the patient's fertilization rate was > 50%. CONCLUSIONS: These results indicate that storage of oocytes in DMSO/sucrose in liquid nitrogen results in superior long-term (> 12 months) preservation of zona receptors for sperm binding and improves oocyte recovery as compared with salt storage at 4 degrees C. Although noninseminated oocytes appear to be optimal for use in the HZA, nonfertilized oocytes can be used successfully if the oocytes originate from an IVF cycle in which the fertilization rate is < or = 50%.

Adult↗
PubMed1993

Nitric oxide and arachidonic acid modulation of calcium currents in postganglionic neurones of avian cultured ciliary ganglia.

1. A study has been made of the modulation of high-voltage activated transient and sustained calcium currents in cultured neurones of avian ciliary ganglia by nitric oxide (NO) and arachidonic acid. 2. Sodium nitroprusside (100 microM) reduced the transient calcium current (ICa) on average by 31% and the sustained ICa by 32% during a test depolarization to +20 mV from a holding potential of -100 mV. This reduction was maintained for at least 30 min following a single application of sodium nitroprusside. 3. L-Arginine (270 microM) reduced the transient ICa on average by 28% and the sustained ICa by 22% and these effects were prevented by the presence of the NO-synthase competitive blocker NG-nitro-L-arginine methylester (L-NAME; 100 microM) in the bathing solution. 4. Arachidonic acid (50 microM) reduced the transient ICa on average by 28% and the sustained ICa by 33%. When added together, arachidonic acid (50 microM) and L-arginine (270 microM) produced the same effects as arachidonic acid alone. 5. Blocking the conversion of arachidonic acid to prostaglandins by addition of indomethacin (20 microM) to the bathing solution did not prevent the depression of either the transient or the sustained calcium current during application of arachidonic acid (50 microM). The effects of arachidonic acid were also not occluded by L-NAME (100 microM) when present in the bathing solution. 6. Inhibiting the biosynthesis of leukotrienes by applying L-663,536 (MK-886; 3 microM) to the bathing solution prevented the depression of both components of ICa during application of arachidonic acid (50 microM). 7. These results indicate that endogenous NO and arachidonic acid pathways are present in parasympathetic ciliary neurones, and that both act to depress high-voltage, gated, calcium channel activity.

Animals↗
PubMed1993

The effect of ions and second messengers on long-term potentiation of chemical transmission in avian ciliary ganglia.

1. The effects of tetanic stimulation of the oculomotor nerve on transmission through the avian ciliary ganglion have been determined by use of the amplitude of the compound action potential recorded in the ciliary nerve, in the presence of hexamethonium (300 microM), as a measure of synaptic efficacy. 2. Tetanic stimulation for 20 s at 30 Hz potentiated the chemical phase of the compound action potential by at least 100% of its control level. This potentiation, reflecting an increase in synaptic efficacy, decayed over two distinct time courses: firstly, a rapid decay with a time constant in the order of minutes, and secondly, a slower decay, representing a smaller potentiation, with a time constant in the order of an hour. The large increase in synaptic efficacy is attributed to post-tetanic potentiation (PTP) whereas the smaller but longer lasting increase is attributed to long-term potentiation (LTP). 3. Higher frequencies of tetanic stimulation gave increased PTP and LTP. 4. In order to test whether the influx of calcium ions into the nerve terminal during the tetanus is likely to be involved in potentiation, facilitation was measured during PTP and LTP. Facilitation was reduced to approximately zero during PTP but recovered to normal values about 15 min into LTP. A requirement for the induction of LTP was shown to be the presence of calcium in the bathing solution. However, blocking synaptic transmission with a high concentration of hexamethonium (3 mM) during the tetanic stimulation did not block the induction of LTP. 5. Application of the muscarinic inhibitor, atropine (2 microM), did not affect the magnitude of PTP or LTP. 5. Application of the muscarinic inhibitor, atropine (2 tM), did not affect the magnitude of PTP or LTP.6. The activator of protein kinase C, phorbol 12,13-dibutyrate (2 microM) potentiated synaptic transmission and reduced the potentiation due to PTP although it did not affect that due to LTP, but the inhibitor of this kinase, staurosporine (0.5 microM), partially blocked the appearance of LTP without affecting PTP after the tetanus.7. An inhibitor of calmodulin, W-7 (5 microM), reversibly blocked the appearance of LTP significantly after a tetanus although the size of PTP was not affected.8. The results presented here suggest that the initiation of LTP in the ciliary ganglion is due to an influx of calcium ions into the calyciform nerve terminal during the tetanus and that the mechanism for LTP involves a calcium-calmodulin-dependent process.

Action Potentials↗