scholarly journals Presynaptic facilitation at the crayfish neuromuscular junction. Role of calcium-activated potassium conductance.

1991 ◽  
Vol 98 (6) ◽  
pp. 1181-1196 ◽  
Author(s):  
S Sivaramakrishnan ◽  
M S Brodwick ◽  
G D Bittner
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Time Course ◽  
Potassium Conductance ◽  
Early Time ◽  
Release Mechanism ◽  
Free Calcium ◽  
Test Pulse ◽  
Current Pulses ◽  
Calcium Activated Potassium Conductance

Membrane potential was recorded intracellularly near presynaptic terminals of the excitor axon of the crayfish opener neuromuscular junction (NMJ), while transmitter release was recorded postsynaptically. This study focused on the effects of a presynaptic calcium-activated potassium conductance, gK(Ca), on the transmitter release evoked by single and paired depolarizing current pulses. Blocking gK(Ca) by adding tetraethylammonium ion (TEA; 5-20 mM) to a solution containing tetrodotoxin and aminopyridines caused the relation between presynaptic potential and transmitter release to steepen and shift to less depolarized potentials. When two depolarizing current pulses were applied at 20-ms intervals with gK(Ca) not blocked, the presynaptic voltage change to the second (test) pulse was inversely related to the amplitude of the first (conditioning) pulse. This effect of the conditioning prepulse on the response to the test pulse was eliminated by 20 mM TEA and by solutions containing 0 mM Ca2+/1 mM EGTA, suggesting that the reduction in the amplitude of the test pulse was due to activation of gK(Ca) by calcium remaining from the conditioning pulse. In the absence of TEA, facilitation of transmitter release evoked by a test pulse increased as the conditioning pulse grew from -40 to -20 mV, but then decreased with further increase in the conditioning depolarization. A similar nonmonotonic relationship between facilitation and the amplitude of the conditioning depolarization was reported in previous studies using extracellular recording, and interpreted as supporting an additional voltage-dependent step in the activation of transmitter release. We suggest that this result was due instead to activation of a gK(Ca) by the conditioning depolarization, since facilitation of transmitter release increased monotonically with the amplitude of the conditioning depolarization, and the early time course of the decay of facilitation was prolonged when gK(Ca) was blocked. The different time courses for decay of the presynaptic potential (20 ms) and facilitation (greater than 50 ms) suggest either that residual free calcium does not account for facilitation at the crayfish NMJ or that the transmitter release mechanism has a markedly higher affinity or stoichiometry for internal free calcium than does gK(Ca). Finally, our data suggest that the calcium channels responsible for transmitter release at the crayfish NMJ are not of the L, N, or T type.

Differences in presynaptic action of 4-aminopyridine and tetraethylammonium at frog neuromuscular junction

1987 ◽  
Vol 65 (5) ◽  
pp. 747-752 ◽  
Author(s):  
M. I. Glavinović
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Action Potentials ◽  
Time Course ◽  
Potassium Conductance ◽  
Frog Neuromuscular Junction ◽  
Quantal Content ◽  
Low Concentrations ◽  
Voltage Dependent ◽  
Intracellular Ca

4-Aminopyridine markedly potentiates transmitter release at the frog cutaneous pectoris neuromuscular junction by increasing the quantal content even when applied at low concentrations (5–20 μM). This enhancement of transmitter release is associated with greater minimum synaptic latency, but the dispersion of the synaptic latencies does not appear much affected. This is in contrast with the action of tetraethylammonium (0.2–0.5 mM) in which case similar enhancement of transmitter release results not only in larger minimum synaptic latency but also in greater dispersion of the synaptic latencies. The time course of transmitter release associated with enhanced transmitter output is hence much more prolonged in the presence of tetraethylammonium than 4-aminopyridine, at least for low concentrations of 4-aminopyridine (5–20 μM). This indicates that their presynaptic actions differ significantly. This conclusion is further strengthened by the finding that unlike tetraethylammonium, 4-aminopyridine induces bursts of release, presumably by producing multiple action potentials in the nerve terminal. Tetraethylammonium probably acts by blocking the delayed potassium conductance, but the blockade of Ca2+-activated K+ conductance cannot be excluded. 4-Aminopyridine, however, probably blocks the fast inactivating (IA) K+ current, but it also may be acting directly on the voltage-dependent Ca2+ conductance or on the intracellular Ca2+ buffering.

Adrenal Chromaffin Cells Exhibit Impaired Granule Trafficking in NCAM Knockout Mice

2005 ◽  
Vol 94 (2) ◽  
pp. 1037-1047 ◽  
Author(s):  
Shyue-An Chan ◽  
Luis Polo-Parada ◽  
Lynn T. Landmesser ◽  
Corey Smith
Keyword(s):  
Neuromuscular Junction ◽  
Knockout Mice ◽  
Transmitter Release ◽  
Chromaffin Cells ◽  
Vesicle Trafficking ◽  
Catecholamine Release ◽  
Neuroendocrine Cells ◽  
Release Mechanism ◽  
General Role ◽  
Releasable Pool

Neural cell adhesion molecule (NCAM) plays several critical roles in neuron path-finding and intercellular communication during development. In the clinical setting, serum NCAM levels are altered in both schizophrenic and autistic patients. NCAM knockout mice have been shown to exhibit deficits in neuronal functions including impaired hippocampal long term potentiation and motor coordination. Recent studies in NCAM null mice have indicated that synaptic vesicle trafficking and active zone targeting are impaired, resulting in periodic synaptic transmission failure under repetitive physiological stimulation. In this study, we tested whether NCAM plays a role in vesicle trafficking that is limited to the neuromuscular junction or whether it may also play a more general role in transmitter release from other cell systems. We tested catecholamine release from neuroendocrine chromaffin cells in the mouse adrenal tissue slice preparation. We utilize electrophysiological and electrochemical measures to assay granule recruitment and targeting in wild-type and NCAM −/− mice. Our data show that NCAM −/− mice exhibit deficits in normal granule trafficking between the readily releasable pool and the highly release-competent immediately releasable pool. This defect results in a decreased rate of granule fusion and thus catecholamine release under physiological stimulation. Our data indicate that NCAM plays a basic role in the transmitter release mechanism in neuroendocrine cells through mediation of granule recruitment and is not limited to the neuromuscular junction and central synapse active zones.

scholarly journals Calcium-activated potassium conductance in presynaptic terminals at the crayfish neuromuscular junction.

1991 ◽  
Vol 98 (6) ◽  
pp. 1161-1179 ◽  
Author(s):  
S Sivaramakrishnan ◽  
G D Bittner ◽  
M S Brodwick
Keyword(s):  
Neuromuscular Junction ◽  
Potassium Conductance ◽  
Presynaptic Terminal ◽  
Constant Current ◽  
Delayed Rectifier ◽  
Presynaptic Terminals ◽  
Potassium Conductances ◽  
Constant Current Pulse ◽  
Calcium Activated Potassium Conductance ◽  
Tetraethylammonium Ions

Membrane potential changes that typically evoke transmitter release were studied by recording intracellularly from the excitor axon near presynaptic terminals of the crayfish opener neuromuscular junction. Depolarization of the presynaptic terminal with intracellular current pulses activated a conductance that caused a decrease in depolarization during the constant current pulse. This conductance was identified as a calcium-activated potassium conductance, gK(Ca), by its disappearance in a zero-calcium/EGTA medium and its block by cadmium, barium, tetraethylammonium ions, and charybdotoxin. In addition to gK(Ca), a delayed rectifier potassium conductance (gK) is present in or near the presynaptic terminal. Both these potassium conductances are involved in the repolarization of the membrane during a presynaptic action potential.

The effects of 4-aminopyridine and tetraethylammonium on the kinetics of transmitter release at the mammalian neuromuscular synapse

1989 ◽  
Vol 67 (9) ◽  
pp. 1045-1050 ◽  
Author(s):  
David A. Saint
Keyword(s):  
Action Potential ◽  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Time Course ◽  
Probability Function ◽  
Neuromuscular Synapse ◽  
Potassium Conductance ◽  
Presynaptic Membrane ◽  
Electrochemical Gradient ◽  
Kinetics Of

The effect of 4-aminopyridine and tetraethylammonium on the time course of neurotransmitter release was examined at the neuromuscular junction using a computer-aided method which directly measured the time of occurrence of individual quanta. It is apparent that the action of 4-aminopyridine, at concentrations of 0.1 to 1 mM, when examined in isolation from other experimental manipulations, is to cause a greatly enhanced probability of release at times subsequent to the time over which release normally occurs. In contrast to previous reports of an increased latency of release, however, the probability of release in the initial phase is essentially unchanged, i.e., there is no evidence of an increased latency of release caused by 4-aminopyridine. Similar results were obtained with tetraethylammonium, although the prolongation of release was much less, even at a concentration of 1 mM. The results are consistent with the view that the predominant action of 4-aminopyridine is to block the potassium conductance responsible for repolarization of the action potential and hence cause a prolonged Ca2+ current. The action of tetraethylammonium is consistent with the block of a different K+ conductance, with consequent enhancement of action potential effectiveness, but with little prolongation of release. The observation of multiple peaks, or oscillations in the release probability function at high (ca. 1 mM) concentrations of 4-aminopyridine, may be related, as is suggested, to oscillations of presynaptic membrane potential, or perhaps to changes in the electrochemical gradient for Ca2+ influx.Key words: transmitter release, 4-aminopyridine, tetraethylammonium, synapse, excitation-secretion coupling, nerve terminal.

Presynaptic effects of a trinitrobenzene analogue at the frog neuromuscular junction

1996 ◽  
Vol 76 (3) ◽  
pp. 1735-1743 ◽  
Author(s):  
M. Osanai ◽  
A. Tsuji ◽  
N. Suzuki ◽  
H. Kijima
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Time Course ◽  
Control Level ◽  
Protein S ◽  
Specific Protein ◽  
Frog Neuromuscular Junction ◽  
Short Term ◽  
Similar Time ◽  
Presynaptic Nerve Terminal

1. Application of 0.15 mM 1-(hydroxyethylamino)-2,4,6-trinitrobenzene (HEATNB) to the frog neuromuscular junction induced a marked increase (4.0-fold) in the amplitude of nerve-evoked end-plate potentials (EPPs) obtained from intracellular and extracellular records, but only a slight increase (1.9-fold) in the frequency of miniature EPPs (MEPPs) obtained from intracellular records. The effects of HEATNB on EPP amplitude and MEPP frequency showed a similar time course, reaching a plateau level approximately 40 min after the start of application and returning to the control level after wash. The difference in the effects of HEATNB on EPP and MEPP frequency suggests that it specifically enhances synchronous transmitter release. 2. Comparing the effects and structure of HEATNB with those of 2,4,6-trinitrobenzene-1-sulfonic acid, we conclude that the observed increase in transmitter release is due to the effects of the trinitrobenzene moiety of those reagents. 3. The distribution of MEPP amplitude was unchanged by HEATNB treatment, indicating that its effects are presynaptic. 4. Among four components of short-term synaptic plasticity, HEATNB greatly decreased (approximately 70%) augmentation and increased (approximately 50%) potentiation, but had little effect on fast and slow facilitations. These results suggest that each of the short-term plasticities has a different mechanism and that HEATNB affects the same mechanisms as those of augmentation. 5. Even when a calcium chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, was loaded into the presynaptic nerve terminal, the effects of HEATNB were not changed in nature, suggesting that effects of HEATNB persist independently of intracellular Ca2+ concentration. 6. These observations suggest that HEATNB may affect specific protein(s) involved primarily in synchronous transmitter release and not asynchronous release.

scholarly journals A Cyclic Adenosine Monophosphate Link in the Catecholamine Enhancement of Transmitter Release at the Neuromuscular Junction

1974 ◽  
Vol 63 (5) ◽  
pp. 609-624 ◽  
Author(s):  
Michael D. Miyamoto ◽  
Bruce McL. Breckenridge
Keyword(s):  
Neuromuscular Junction ◽  
Nerve Terminal ◽  
Transmitter Release ◽  
Time Course ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Dibutyryl Camp ◽  
Miniature Endplate Potentials ◽  
Endplate Potentials

The frequency of miniature endplate potentials (mepps) in rat diaphragms was markedly increased by epinephrine and norepinephrine in preparations exposed to 15 mM K+. The effect was rapid in onset but gradually declined during continued exposure to the catecholamines. N6, O2'-dibutyryl adenosine 3',5'-monophosphate (dibutyryl-cAMP) also caused transient frequency increases resembling in time-course those observed with catecholamines. Contrary to previous reports, catecholamines and dibutyryl-cAMP had little effect on mepp frequency in preparations not treated with K+. Sustained increases with theophylline and decreases with adenosine were found in both K+-treated and untreated preparations. Analysis of the data obtained with catecholamines showed the intensity of the response to be a function of nerve terminal polarization. The inability of catecholamines and dibutyryl-cAMP to affect mepp frequency of untreated preparations argues against an obligatory role for cAMP in the neurosecretory mechanism. The findings are consistent with an action of catecholamines and cAMP in the regulation of transmitter release at fatigued preparations.

Suppression of transmitter release at the neuromuscular junction

1977 ◽  
Vol 196 (1125) ◽  
pp. 465-469 ◽  
Keyword(s):  
Neuromuscular Junction ◽  
Transmitter Release ◽  
Current Flow ◽  
Motor Nerve ◽  
Potassium Currents ◽  
Current Pulses ◽  
Squid Giant Synapse ◽  
Giant Synapse ◽  
Endplate Potentials ◽  
Sodium And Potassium

Tetrodotoxin and tetraethylammonium were used on frog and rat endplates, to inhibit voltage-activated sodium and potassium currents. Under these conditions, large endplate potentials can be evoked by applying super-threshold depolarizing current pulses (of 50-100 ms duration) to the motor nerve endings. When the current intensity is increased several­ fold above threshold, the response is suppressed during the current flow, and delayed until the pulse is terminated. This phenomenon is similar to and complements earlier observations on the squid giant synapse.

Inward rectification in rat nucleus accumbens neurons

1989 ◽  
Vol 62 (6) ◽  
pp. 1280-1286 ◽  
Author(s):  
N. Uchimura ◽  
E. Cherubini ◽  
R. A. North
Keyword(s):  
Steady State ◽  
Nucleus Accumbens ◽  
Time Course ◽  
Potassium Conductance ◽  
Resting Potential ◽  
Inward Rectification ◽  
Resting Membrane Potential ◽  
Potential Range ◽  
Inward Current ◽  
Rat Nucleus Accumbens

1. Intracellular recordings were made from neurons in slices cut from the rat nucleus accumbens septi. Membrane currents were measured with a single-electrode voltage-clamp amplifier in the potential range -50 to -140 mV. 2. In control conditions (2.5 mM potassium), the resting membrane potential of the neurons was -83.4 +/- 1.1 (SE) mV (n = 157). Steady state membrane conductance was voltage dependent, being 34.8 +/- 1.7 nS (n = 25) at -100 mV and 8.0 +/- 0.7 nS (n = 25) at -60 mV. 3. Barium (1 microM) markedly reduced the inward rectification and caused a small inward current (40.6 +/- 8.7 pA, n = 8) at the resting potential. These effects became larger with higher barium concentrations, and, in 100 microM barium, the current-voltage relation was straight. 4. The block of the inward current by barium (at -130 mV) occurred with an exponential time course; the time constant was approximately 1 s at 1 microM barium and less than 90 ms with 100 microM. Strontium had effects similar to those of barium, but 1000-fold higher concentrations were required. Cesium chloride (2 mM) and rubidium chloride (2 mM) also blocked the inward rectification; their action reached steady state within 50 ms. 5. It is concluded that the nucleus accumbens neurons have a potassium conductance with many features of a typical inward rectifier and that this contributes to the potassium conductance at the resting potential.

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