Modulation of Transmitter Release by Action Potential Duration at the Hippocampal CA3-CA1 Synapse

1999 ◽  
Vol 81 (1) ◽  
pp. 288-298 ◽  
Author(s):  
Jing Qian ◽  
Peter Saggau
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Action Potential Duration ◽  
Transmitter Release ◽  
Neurotransmitter Release ◽  
Channel Blocker ◽  
Transmission Curve ◽  
Similar Reduction ◽  
Voltage Dependent ◽  
Hippocampal Ca3

Qian, Jing and Peter Saggau. Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse. J. Neurophysiol. 81: 288–298, 1999. Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynaptic Ca2+ influx. This increase of Ca2+ influx appeared to be much less effective in enhancing transmitter release than raising the extracellular Ca2+ concentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effective Ca2+ concentration near the Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N-type Ca2+ channel blocker ωCgTx GVIA was much less effective in blocking transmitter release. This phenomenon was not simply due to a saturation of the release machinery by the increased overall Ca2+ influx because a similar reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker Cd2+ resulted in much more inhibition of transmitter release. Rather, the different potencies of ω-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca2+ sensor is possibly located at a distance from a cluster of Ca2+ channels such that it is sensitive to the location of Ca2+ channels within the cluster.

scholarly journals Inhibition of Ca2+-activated large-conductance K+ channel activity alters synaptic AMPA receptor phenotype in mouse cerebellar stellate cells

2011 ◽  
Vol 106 (1) ◽  
pp. 144-152 ◽  
Author(s):  
Yu Liu ◽  
Iaroslav Savtchouk ◽  
Shoana Acharjee ◽  
Siqiong June Liu
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Channel Blocker ◽  
Stellate Cells ◽  
Bk Channels ◽  
Bk Channel ◽  
K Channel ◽  
Duration Of Action

Many fast-spiking inhibitory interneurons, including cerebellar stellate cells, fire brief action potentials and express α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors (AMPAR) that are permeable to Ca2+ and do not contain the GluR2 subunit. In a recent study, we found that increasing action potential duration promotes GluR2 gene transcription in stellate cells. We have now tested the prediction that activation of potassium channels that control the duration of action potentials can suppress the expression of GluR2-containing AMPARs at stellate cell synapses. We find that large-conductance Ca2+-activated potassium (BK) channels mediate a large proportion of the depolarization-evoked noninactivating potassium current in stellate cells. Pharmacological blockade of BK channels prolonged the action potential duration in postsynaptic stellate cells and altered synaptic AMPAR subtype from GluR2-lacking to GluR2-containing Ca2+-impermeable AMPARs. An L-type channel blocker abolished an increase in Ca2+ entry that was associated with spike broadening and also prevented the BK channel blocker-induced switch in AMPAR phenotype. Thus blocking BK potassium channels prolongs the action potential duration and increases the expression of GluR2-containing receptors at the synapse by enhancing Ca2+ entry in cerebellar stellate cells.

scholarly journals Calcium influx through If channels in rat ventricular myocytes

2007 ◽  
Vol 292 (3) ◽  
pp. C1147-C1155 ◽  
Author(s):  
Xiao Yu ◽  
Xiao-Wei Chen ◽  
Peng Zhou ◽  
Lijun Yao ◽  
Tao Liu ◽  
...  
Keyword(s):  
Action Potential ◽  
Cardiac Myocytes ◽  
Action Potential Duration ◽  
Channel Blocker ◽  
Ventricular Myocytes ◽  
Spontaneously Hypertensive Rat ◽  
Calcium Influx ◽  
Hek293 Cells ◽  
Hcn Channels ◽  
Rat Ventricular Myocytes

The hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, or cardiac ( If)/neuronal ( Ih) time- and voltage-dependent inward cation current channels, are conventionally considered as monovalent-selective channels. Recently we discovered that calcium ions can permeate through HCN4 and Ih channels in neurons. This raises the possibility of Ca2+ permeation in If, the Ih counterpart in cardiac myocytes, because of their structural homology. We performed simultaneous measurement of fura-2 Ca2+ signals and whole cell currents produced by HCN2 and HCN4 channels (the 2 cardiac isoforms present in ventricles) expressed in HEK293 cells and by If in rat ventricular myocytes. We observed Ca2+ influx when HCN/ If channels were activated. Ca2+ influx was increased with stronger hyperpolarization or longer pulse duration. Cesium, an If channel blocker, inhibited If and Ca2+ influx at the same time. Quantitative analysis revealed that Ca2+ flux contributed to ∼0.5% of current produced by the HCN2 channel or If. The associated increase in Ca2+ influx was also observed in spontaneously hypertensive rat (SHR) myocytes in which If current density is higher than that of normotensive rat ventricle. In the absence of EGTA (a Ca2+ chelator), preactivation of If channels significantly reduced the action potential duration, and the effect was blocked by another selective If channel blocker, ZD-7288. In the presence of EGTA, however, preactivation of If channels had no effects on action potential duration. Our data extend our previous discovery of Ca2+ influx in Ih channels in neurons to If channels in cardiac myocytes.

scholarly journals FMRP Regulates Neurotransmitter Release and Synaptic Information Transmission by Modulating Action Potential Duration via BK Channels

Neuron ◽  
2013 ◽  
Vol 78 (1) ◽  
pp. 205 ◽  
Author(s):  
Pan-Yue Deng ◽  
Ziv Rotman ◽  
Jay A. Blundon ◽  
Yongcheol Cho ◽  
Jianmin Cui ◽  
...  
Keyword(s):  
Action Potential ◽  
Information Transmission ◽  
Action Potential Duration ◽  
Neurotransmitter Release ◽  
Bk Channels

Postnatal Maturation of Rat Hypothalamoneurohypophysial Neurons: Evidence for a Developmental Decrease in Calcium Entry During Action Potentials

1997 ◽  
Vol 77 (1) ◽  
pp. 260-271 ◽  
Author(s):  
H. Widmer ◽  
H. Amerdeil ◽  
P. Fontanaud ◽  
M. G. Desarménien
Keyword(s):  
Action Potential ◽  
Decay Time ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Potassium Current ◽  
Calcium Entry ◽  
Calcium Currents ◽  
Postnatal Maturation ◽  
Boltzmann Function ◽  
Voltage Dependent

Widmer, H., H. Amerdeil, P. Fontanaud, and M. G. Desarménien. Postnatal maturation of rat hypothalamoneurohypophysial neurons: evidence for a developmental decrease in calcium entry during action potentials. J. Neurophysiol. 77: 260–271, 1997. Action potentials and voltage-gated currents were studied in acutely dissociated neurosecretory cells from the rat supraoptic nucleus during the first three postnatal weeks (PW1–PW3), a period corresponding to the final establishment of neuroendocrine relationships. Action potential duration (at half maximum) decreased from 2.7 to 1.8 ms; this was attributable to a decrease in decay time. Application of cadmium (250 μM) reduced the decay time by 43% at PW1 and 21% at PW3, indicating that the contribution of calcium currents to action potentials decreased during postnatal development. The density of high-voltage-activated calcium currents increased from 4.4 to 10.1 pA/pF at postnatal days 1–5 and 11–14, respectively. The conductance density of sustained potassium current, measured at +20 mV, increased from 0.35 (PW1) to 0.53 (PW3) nS/pF. The time to half-maximal amplitude did not change. Conductance density and time- and voltage-dependent inactivation of the transient potassium current were stable from birth. At PW1, the density and time constant of decay (measured at 0 mV) were 0.29 nS/pF ( n = 12) and 17.9 ms ( n = 10), respectively. Voltage-dependent properties and density (1.1 nS/pF) of the sodium current did not change postnatally. During PW1, fitting the mean activation data with a Boltzmann function gave a half-activation potential of −25 mV. A double Boltzman equation was necessary to adequately fit the inactivation data, suggesting the presence of two populations of sodium channels. One population accounted for ∼14% of the channels, with a half-inactivation potential of −86 mV; the remaining population showed a half-inactivation potential of −51 mV. A mathematical model, based on Hodgkin-Huxley equations, was used to assess the respective contributions of individual currents to the action potential. When the densities of calcium and sustained potassium currents were changed from immature to mature values, the decay time of the action potentials generated with the model decreased from 2.85 to 1.95 ms. A similar reduction was obtained when only the density of the potassium current was increased. Integration of the calcium currents generated during mature and immature action potentials demonstrated a significant decrease in calcium entry during development. We conclude that the developmental reduction of the action potential duration 1) is a consequence of the developmentally regulated increase in a sustained potassium current and 2) leads to a reduction of the participation of calcium currents in the action potential, resulting in a decreased amount of calcium entering the cell during each action potential.

scholarly journals Voltage control of Ca2+ permeation through N-type calcium (CaV2.2) channels

2014 ◽  
Vol 144 (3) ◽  
pp. 207-220 ◽  
Author(s):  
Zafir Buraei ◽  
Haoya Liang ◽  
Keith S. Elmslie
Keyword(s):  
Binding Sites ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Channel Blocker ◽  
Cellular Functions ◽  
Voltage Gated ◽  
High Affinity ◽  
Step Model ◽  
Independent Test ◽  
Voltage Dependent

Voltage-gated calcium (CaV) channels deliver Ca2+ to trigger cellular functions ranging from cardiac muscle contraction to neurotransmitter release. The mechanism by which these channels select for Ca2+ over other cations is thought to involve multiple Ca2+-binding sites within the pore. Although the Ca2+ affinity and cation preference of these sites have been extensively investigated, the effect of voltage on these sites has not received the same attention. We used a neuronal preparation enriched for N-type calcium (CaV2.2) channels to investigate the effect of voltage on Ca2+ flux. We found that the EC50 for Ca2+ permeation increases from 13 mM at 0 mV to 240 mM at 60 mV, indicating that, during permeation, Ca2+ ions sense the electric field. These data were nicely reproduced using a three-binding-site step model. Using roscovitine to slow CaV2.2 channel deactivation, we extended these measurements to voltages <0 mV. Permeation was minimally affected at these hyperpolarized voltages, as was predicted by the model. As an independent test of voltage effects on permeation, we examined the Ca2+-Ba2+ anomalous mole fraction (MF) effect, which was both concentration and voltage dependent. However, the Ca2+-Ba2+ anomalous MF data could not be reproduced unless we added a fourth site to our model. Thus, Ca2+ permeation through CaV2.2 channels may require at least four Ca2+-binding sites. Finally, our results suggest that the high affinity of Ca2+ for the channel helps to enhance Ca2+ influx at depolarized voltages relative to other ions (e.g., Ba2+ or Na+), whereas the absence of voltage effects at negative potentials prevents Ca2+ from becoming a channel blocker. Both effects are needed to maximize Ca2+ influx over the voltages spanned by action potentials.

scholarly journals A Theory of Synaptic Transmission

2020 ◽  
Author(s):  
Bin Wang ◽  
Olga Dudko
Keyword(s):  
Experimental Data ◽  
Action Potential ◽  
Synaptic Transmission ◽  
Neurotransmitter Release ◽  
Molecular Mechanisms ◽  
Synaptic Function ◽  
Universal Curve ◽  
Universal Scaling ◽  
Neuronal Communication ◽  
Key Characteristics

Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters into the synapse within just milliseconds of the action potential. We present an analytic theory that captures general principles of synaptic transmission while generating concrete predictions for particular synapses. A universal scaling is established, and demonstrated through a collapse of experimental data from different synapses onto a universal curve. The theory shows how key characteristics of synaptic function -- plasticity, fidelity, and efficacy -- emerge from molecular mechanisms of neurotransmitter release machinery.

scholarly journals Calcium-independent but voltage-dependent secretion (CiVDS) mediates synaptic transmission in a mammalian central synapse

2021 ◽  
Author(s):  
Yuan Wang ◽  
Rong Huang ◽  
Zuying Chai ◽  
Changhe Wang ◽  
Xingyu Du ◽  
...  
Keyword(s):  
Action Potential ◽  
Synaptic Transmission ◽  
Sympathetic Neurons ◽  
Fusion Pore ◽  
Short Term ◽  
Vesicle Recycling ◽  
Dorsal Horn Neurons ◽  
Central Synapse ◽  
Voltage Dependent ◽  
Intracellular Ca

A central principle of synaptic transmission is that action potential induced presynaptic neurotransmitter release occurs exclusively via Ca2+ dependent secretion (CDS). T he discovery and mechanistic investigations of Ca2+ independent but voltage dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons, (1) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS up to 87%) and CDS; (2) CiVDS EPSC s are in dependent of extracellular and intracellular Ca2+; (3) CiVDS is >100 times faster than CDS in vesicle recycling with much less short term depression; 4) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity induced EPSCs is mediated by CiVDS in a central synapse.

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