Primary and Secondary Regulation of Quantal Transmitter Release: Calcium and Sodium

1980 ◽  
Vol 89 (1) ◽  
pp. 5-18
Author(s):  
RAMI RAHAMIMOFF ◽  
AHARON LEV-TOV ◽  
HALINA MEIRI
Keyword(s):  
Action Potential ◽  
Nerve Terminal ◽  
Transmitter Release ◽  
Surface Membrane ◽  
Nerve Impulse ◽  
High Frequency Stimulation ◽  
Extracellular Medium ◽  
Presynaptic Nerve Terminal ◽  
Virtual Absence ◽  
Frequency Stimulation

Calcium is the prime regulator of quantal acetylcholine liberation at the neuromuscular junction; its entry through the presynaptic membrane and the level of free [Ca]ln most probably determine the number of transmitter quanta liberated by the nerve impulse. The level of free [Ca]ln, in turn, is controlled by a number of subcellular elements: mitochondria, endoplasmic reticulum, vesicles, macromolecules and the surface membrane. The action potential induced calcium entry is not the only factor responsible for coupling nerve terminal depolarization with increased transmitter release; increased transmitter release occurs also in the virtual absence of calcium ions in the extracellular medium, when a reversed electrochemical gradient for calcium probably exists during action potential activity. Several lines of evidence suggest that the entry of sodium ions is responsible for this augmented transmitter release: the tetanic potentiation observed under reversed calcium gradient is blocked by tetrodotoxin; tetanic and post-tetanic potentiation are augmented and prolonged by ouabain; the amplitude of the extracellular nerve action potential is reduced with high-frequency stimulation, in parallel with increased spontaneous quantal release. In addition, sodium-filled egg-lecithine liposomes augment quantal liberation. The augmentory effect of sodium on transmitter release is probably due to an intracellular calcium translocation, since no preferred timing after the action potential is observed. Thus the level of [Na]ln in the presynaptic nerve terminal can control indirectly the efficiency of synaptic transmission.

scholarly journals Multitude of ion channels in regulation of transmitter release

1999 ◽  
Vol 354 (1381) ◽  
pp. 281-288 ◽  
Author(s):  
Rami Rahamimoff ◽  
Alexander Butkevich ◽  
Dessislava Duridanova ◽  
Ronit Ahdut ◽  
Emanuel Harari ◽  
...  
Keyword(s):  
Ion Channels ◽  
Potassium Channels ◽  
Nerve Terminal ◽  
Transmitter Release ◽  
Synaptic Vesicles ◽  
Chloride Channels ◽  
Surface Membrane ◽  
Structural Basis ◽  
Primary Role ◽  
Presynaptic Nerve Terminal

The presynaptic nerve terminal is of key importance in the communication in the nervous system. Its primary role is to release transmitter quanta on the arrival of an appropriate stimulus. The structural basis of these transmitter quanta are the synaptic vesicles that fuse with the surface membrane of the nerve terminal, to release their content of neurotransmitter molecules and other vesicular components. We subdivide the control of quantal release into two major classes: the processes that take place before the fusion of the synaptic vesicle with the surface membrane (the pre–fusion control) and the processes that occur after the fusion of the vesicle (the post–fusion control). The pre–fusion control is the main determinant of transmitter release. It is achieved by a wide variety of cellular components, among them the ion channels. There are reports of several hundred different ion channel molecules at the surface membrane of the nerve terminal, that for convenience can be grouped into eight major categories. They are the voltage–dependent calcium channels, the potassium channels, the calcium–gated potassium channels, the sodium channels, the chloride channels, the non–selective channels, the ligand gated channels and the stretch–activated channels. There are several categories of intracellular channels in the mitochondria, endoplasmic reticulum and the synaptic vesicles. We speculate that the vesicle channels may be of an importance in the post–fusion control of transmitter release.

Ion Channels in Presynaptic Nerve Terminals and Control of Transmitter Release

1999 ◽  
Vol 79 (3) ◽  
pp. 1019-1088 ◽  
Author(s):  
Alon Meir ◽  
Simona Ginsburg ◽  
Alexander Butkevich ◽  
Sylvia G. Kachalsky ◽  
Igor Kaiserman ◽  
...  
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Nerve Terminal ◽  
Transmitter Release ◽  
Surface Membrane ◽  
Basic Function ◽  
Fine Tuning ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
Presynaptic Nerve Terminals

The primary function of the presynaptic nerve terminal is to release transmitter quanta and thus activate the postsynaptic target cell. In almost every step leading to the release of transmitter quanta, there is a substantial involvement of ion channels. In this review, the multitude of ion channels in the presynaptic terminal are surveyed. There are at least 12 different major categories of ion channels representing several tens of different ion channel types; the number of different ion channel molecules at presynaptic nerve terminals is many hundreds. We describe the different ion channel molecules at the surface membrane and inside the nerve terminal in the context of their possible role in the process of transmitter release. Frequently, a number of different ion channel molecules, with the same basic function, are present at the same nerve terminal. This is especially evident in the cases of calcium channels and potassium channels. This abundance of ion channels allows for a physiological and pharmacological fine tuning of the process of transmitter release and thus of synaptic transmission.

Modification of transmitter release by electrical interference with motor nerve endings

1967 ◽  
Vol 167 (1006) ◽  
pp. 1-7 ◽  
Keyword(s):  
Action Potential ◽  
Nerve Terminal ◽  
Transmitter Release ◽  
Calcium Concentration ◽  
Motor Nerve ◽  
Nerve Impulse ◽  
Nerve Endings ◽  
External Calcium ◽  
Electrical Interference

1. A hyperpolarizing pulse applied through an external microelectrode to a nerve terminal during the falling phase of its action potential can suppress transmitter release; a depolarizing pulse applied during the same period can potentiate the release. 2. The facilitating action of calcium on transmitter release was studied by synchronizing the arrival of the nerve impulse with a rapid increment of the external calcium concentration. Using ionophoretic pulses of calcium, an effect could be produced with very little delay; sometimes the calcium pulse was effective when it preceded the arrival of the nerve impulse by only 1 to 2 ms.

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

2011 ◽  
Vol 300 (2) ◽  
pp. H565-H573 ◽  
Author(s):  
Masahide Harada ◽  
Yukiomi Tsuji ◽  
Yuko S. Ishiguro ◽  
Hiroki Takanari ◽  
Yusuke Okuno ◽  
...  
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
High Frequency Stimulation ◽  
Electrophysiological Properties ◽  
Rate Dependent ◽  
Frequency Stimulation ◽  
And Control

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Neurotransmitter release from high-frequency stimulation of the subthalamic nucleus

2004 ◽  
Vol 101 (3) ◽  
pp. 511-517 ◽  
Author(s):  
Kendall H. Lee ◽  
Su-Youne Chang ◽  
David W. Roberts ◽  
Uhnoh Kim
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Neurotransmitter Release ◽  
High Frequency Stimulation ◽  
Content Type ◽  
Action Potential Frequency ◽  
Frequency Stimulation ◽  
Potential Frequency ◽  
Fine Print ◽  
Stimulation Of

Object. High-frequency stimulation (HFS) delivered through implanted electrodes in the subthalamic nucleus (STN) has become an established treatment for Parkinson disease (PD). The precise mechanism of action of deep brain stimulation (DBS) in the STN is unknown, however. In the present study, the authors tested the hypothesis that HFS within the STN changes neuronal action potential firing rates during the stimulation period by modifying neurotransmitter release. Methods. Intracellular electrophysiological recordings were obtained using sharp electrodes in rat STN neurons in an in vitro slice preparation. A concentric bipolar stimulating electrode was placed in the STN slice, and electrical stimulation (pulse width 50–100 µsec, duration 100–2000 µsec, amplitude 10–500 µA, and frequency 10–200 Hz) was delivered while simultaneously obtaining intracellular recordings from an STN neuron. High-frequency stimulation of the STN either generated excitatory postsynaptic potentials (EPSPs) and increased the action potential frequency or it generated inhibitory postsynaptic potentials and decreased the action potential frequency of neurons within the STN. These effects were blocked after antagonists to glutamate and γ-aminobutyric acid were applied to the tissue slice, indicating that HFS resulted in the release of neurotransmitters. Intracellular recordings from substantia nigra pars compacta (SNc) dopaminergic neurons during HFS of the STN revealed increased generation of EPSPs and increased frequency of action potentials in SNc neurons. Conclusions. During HFS of STN neurons the mechanism of DBS may involve the release of neurotransmitters rather than the primary electrogenic inhibition of neurons.

Transmitter release induced by injection of calcium ions into nerve terminals

1973 ◽  
Vol 183 (1073) ◽  
pp. 421-425 ◽  
Keyword(s):  
Nerve Terminal ◽  
Calcium Ions ◽  
Transmitter Release ◽  
Nerve Terminals ◽  
Presynaptic Nerve Terminal ◽  
External Fluid ◽  
Giant Synapse ◽  
Evoked Transmitter Release

Calcium ions injected into the presynaptic nerve terminal in the giant synapse of the squid, evoked transmitter release while similar doses of Mg and Mn were ineffective. The transmitter release induced by intracellular application was still observed when Ca was replaced in the external fluid by Mn, in spite of the fact that this abolished transmitter release in response to presynaptic depolarization.

scholarly journals The Cannabinoid-Like Compound, VSN16R, Acts on Large Conductance, Ca2+-Activated K+ Channels to Modulate Hippocampal CA1 Pyramidal Neuron Firing

2019 ◽  
Vol 12 (3) ◽  
pp. 104
Author(s):  
Setareh Tabatabaee ◽  
David Baker ◽  
David L. Selwood ◽  
Benjamin J. Whalley ◽  
Gary J. Stephens
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Pyramidal Neurons ◽  
Low Frequency ◽  
Firing Frequency ◽  
High Frequency Stimulation ◽  
Bkca Channel ◽  
Bkca Channels ◽  
Low Frequency Stimulation ◽  
Frequency Stimulation

Large conductance, Ca2+-activated K+ (BKCa) channels are widely expressed in the central nervous system, where they regulate action potential duration, firing frequency and consequential neurotransmitter release. Moreover, drug action on, mutations to, or changes in expression levels of BKCa can modulate neuronal hyperexcitability. Amongst other potential mechanisms of action, cannabinoid compounds have recently been reported to activate BKCa channels. Here, we examined the effects of the cannabinoid-like compound (R,Z)-3-(6-(dimethylamino)-6-oxohex-1-en-1-yl)-N-(1-hydroxypropan-2-yl) benzamide (VSN16R) at CA1 pyramidal neurons in hippocampal ex vivo brain slices using current clamp electrophysiology. We also investigated effects of the BKCa channel blockers iberiotoxin (IBTX) and the novel 7-pra-martentoxin (7-Pra-MarTx) on VSN16R action. VSN16R (100 μM) increased first and second fast after-hyperpolarization (fAHP) amplitude, decreased first and second inter spike interval (ISI) and shortened first action potential (AP) width under high frequency stimulation protocols in mouse hippocampal pyramidal neurons. IBTX (100 nM) decreased first fAHP amplitude, increased second ISI and broadened first and second AP width under high frequency stimulation protocols; IBTX also broadened first and second AP width under low frequency stimulation protocols. IBTX blocked effects of VSN16R on fAHP amplitude and ISI. 7-Pra-MarTx (100 nM) had no significant effects on fAHP amplitude and ISI but, unlike IBTX, shortened first and second AP width under high frequency stimulation protocols; 7-Pra-MarTx also shortened second AP width under low frequency stimulation protocols. However, in the presence of 7-Pra-MarTx, VSN16R retained some effects on AP waveform under high frequency stimulation protocols; moreover, VSN16R effects were revealed under low frequency stimulation protocols. These findings demonstrate that VSN16R has effects in native hippocampal neurons consistent with its causing an increase in initial firing frequency via activation of IBTX-sensitive BKCa channels. The differential pharmacological effects described suggest that VSN16R may differentially target BKCa channel subtypes.

Changes in the Readily Releasable Pool of Transmitter and in Efficacy of Release Induced by High-Frequency Firing at Aplysia Sensorimotor Synapses in Culture

2004 ◽  
Vol 91 (4) ◽  
pp. 1500-1509 ◽  
Author(s):  
Yali Zhao ◽  
Marc Klein
Keyword(s):  
Motor Neuron ◽  
High Frequency ◽  
Transmitter Release ◽  
Action Potentials ◽  
High Frequency Stimulation ◽  
Hypertonic Solution ◽  
Posttetanic Potentiation ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Frequency Stimulation

Synaptic transmission at the sensory neuron-motor neuron synapses of Aplysia, like transmission at many synapses of both vertebrates and invertebrates, is increased after a short burst of high-frequency stimulation (HFS), a phenomenon known as posttetanic potentiation (PTP). PTP is generally attributable to an increase in transmitter release from presynaptic neurons. We investigated whether changes in the readily releasable pool of transmitter (RRP) contribute to the potentiation that follows HFS. We compared the changes in excitatory postsynaptic potentials (EPSPs) evoked with action potentials to changes in the RRP as estimated from the asynchronous transmitter release elicited by a hypertonic solution. The changes in the EPSP were correlated with changes in the RRP, but the changes matched quantitatively only at connections whose initial synaptic strength was greater than the median for all experiments. At weaker connections, the increase in the RRP was insufficient to account for PTP. Weaker connections initially released a smaller fraction of the RRP with each EPSP than stronger ones, and this fraction increased at weaker connections after HFS. Moreover, the initial transmitter release in response to the hypertonic solution was accelerated after HFS, indicating that the increase in the efficacy of release was not restricted to excitation-secretion coupling. Modulation of the RRP and of the efficacy of release thus both contribute to the enhancement of transmitter release by HFS.

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