scholarly journals Evidence that Exocytosis Is Driven by Calcium Entry Through Multiple Calcium Channels in Goldfish Retinal Bipolar Cells

2009 ◽  
Vol 101 (5) ◽  
pp. 2601-2619 ◽  
Author(s):  
Michael Coggins ◽  
David Zenisek

Ribbon-containing neurons represent a subset of neural cells that undergo graded membrane depolarizations rather than Na+-channel evoked action potentials. Bipolar cells of the retina are one type of ribbon-containing neuron and extensive research has demonstrated kinetically distinct pools of vesicles that are released and replenished in a calcium-dependent manner. In this study, we look at the properties of the fastest pool of releasable vesicles in these cells, often referred to as the immediately releasable pool (IRP), to investigate the relationships between vesicle release and calcium channels in these terminals. Using whole cell capacitance measurements, we monitored exocytosis in response to different magnitude and duration depolarizations, with emphasis on physiologically relevant step depolarizations. We find that release rate of the IRP increases superlinearly with membrane potential and that the IRP is sensitive to elevated EGTA concentrations in a membrane-potential–dependent manner across the physiological range of membrane potentials. Our results are best explained by a model in which multiple Ca2+ channels act in concert to drive exocytosis of a single synaptic vesicle. Pooling calcium entering through many calcium channels may be important for reducing stochastic noise in neurotransmitter release associated with the opening of individual calcium channels.

1999 ◽  
Vol 115 (1) ◽  
pp. 3-16 ◽  
Author(s):  
D.A. Kraaij ◽  
H. Spekreijse ◽  
M. Kamermans

Cones in the vertebrate retina project to horizontal and bipolar cells and the horizontal cells feedback negatively to cones. This organization forms the basis for the center/surround organization of the bipolar cells, a fundamental step in the visual signal processing. Although the surround responses of bipolar cells have been recorded on many occasions, surprisingly, the underlying surround-induced responses in cones are not easily detected. In this paper, the nature of the surround-induced responses in cones is studied. Horizontal cells feed back to cones by shifting the activation function of the calcium current in cones to more negative potentials. This shift increases the calcium influx, which increases the neurotransmitter release of the cone. In this paper, we will show that under certain conditions, in addition to this increase of neurotransmitter release, a calcium-dependent chloride current will be activated, which polarizes the cone membrane potential. The question is, whether the modulation of the calcium current or the polarization of the cone membrane potential is the major determinant for feedback-mediated responses in second-order neurons. Depolarizing light responses of biphasic horizontal cells are generated by feedback from monophasic horizontal cells to cones. It was found that niflumic acid blocks the feedback-induced depolarizing responses in cones, while the shift of the calcium current activation function and the depolarizing biphasic horizontal cell responses remain intact. This shows that horizontal cells can feed back to cones, without inducing major changes in the cone membrane potential. This makes the feedback synapse from horizontal cells to cones a unique synapse. Polarization of the presynaptic (horizontal) cell leads to calcium influx in the postsynaptic cell (cone), but due to the combined activity of the calcium current and the calcium-dependent chloride current, the membrane potential of the postsynaptic cell will be hardly modulated, whereas the output of the postsynaptic cell will be strongly modulated. Since no polarization of the postsynaptic cell is needed for these feedback-mediated responses, this mechanism of synaptic transmission can modulate the neurotransmitter release in single synaptic terminals without affecting the membrane potential of the entire cell.


1993 ◽  
Vol 70 (2) ◽  
pp. 758-764 ◽  
Author(s):  
E. Garcia ◽  
A. Benitez ◽  
C. G. Onetti

1. An electrophysiological study of the D-glucose sensitivity of X-organ (XO) neurosecretory cell bodies in crayfish was carried out with the use of microelectrodes, perforated, and cell-attached patch-clamp techniques. 2. Glucose depolarizes the membrane potential of XO cells in a concentration-dependent manner. 3. Depolarization produced by glucose initiates a change in the pattern of electrical activity. Silent cells began to discharge action potentials. When bursting cells are depolarized by glucose, their action potentials are no longer grouped in bursts or disappear entirely. 4. Although the membrane potential returns to its initial value after removing glucose from the bath, discharge patterns of the cells may remain different. This suggests that besides the depolarizing effect, once the cells have been exposed to glucose, the sugar switches on a process that is maintained for a long time. 5. Glucose produced a reduction of membrane steady-state conductance, and a shift of reversal potential of membrane currents to a more positive value. 6. Depolarization induced by D-glucose appears to be related with a closure of potassium channels. 7. Glucose effect was thought to be generated by a product of metabolism that would act as intracellular mediator.


2006 ◽  
Vol 34 (5) ◽  
pp. 887-893 ◽  
Author(s):  
F. Van Petegem ◽  
D.L. Minor

Voltage-gated calcium channels (CaVs) are large (∼0.5 MDa), multisubunit, macromolecular machines that control calcium entry into cells in response to membrane potential changes. These molecular switches play pivotal roles in cardiac action potentials, neurotransmitter release, muscle contraction, calcium-dependent gene transcription and synaptic transmission. CaVs possess self-regulatory mechanisms that permit them to change their behaviour in response to activity, including voltage-dependent inactivation, calcium-dependent inactivation and calcium-dependent facilitation. These processes arise from the concerted action of different channel domains with CaV β-subunits and the soluble calcium sensor calmodulin. Until recently, nothing was known about the CaV structure at high resolution. Recent crystallographic work has revealed the first glimpses at the CaV molecular framework and set a new direction towards a detailed mechanistic understanding of CaV function.


1987 ◽  
Vol 252 (4) ◽  
pp. H867-H871
Author(s):  
D. L. Kunze

A preparation of cells isolated from the medial and dorsal nuclei of the solitary tract of the medulla of adult guinea pigs was developed to examine the electrical properties of neurons isolated from an area of the central nervous system which is involved in the control of arterial pressure and heart rate. Bipolar cells of approximately 10 microns diameter were obtained on enzymatic dispersion. The cells were studied with the use of the patch technique for whole cell recording. Action potentials were elicited by depolarizing pulses in the presence of 10(-5) M tetrodotoxin which blocked a sodium-dependent current. These action potentials were calcium dependent and were eliminated by adding 1 mM Cd to the bath. In all cells studied, two voltage-dependent components to the calcium current were identified. In 10 mM Ca a high-threshold component activated at approximately -20 mV from holding potentials of -30 mV. A second lower threshold component was activated at -40 mV from more negative holding potentials of -80 mV. The low-threshold component was rapidly inactivating, whereas the high-threshold current slowly inactivated. The peak amplitudes of the two components were similar. Both components were blocked by 1 mM Cd. A role for the low-threshold calcium current in generating repetitive activity is postulated.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2574
Author(s):  
Rong-Shan Yan ◽  
Xiong-Li Yang ◽  
Yong-Mei Zhong ◽  
Dao-Qi Zhang

Correlated spontaneous activity in the developing retina (termed “retinal waves”) plays an instructive role in refining neural circuits of the visual system. Depolarizing (ON) and hyperpolarizing (OFF) starburst amacrine cells (SACs) initiate and propagate cholinergic retinal waves. Where cholinergic retinal waves stop, SACs are thought to be driven by glutamatergic retinal waves initiated by ON-bipolar cells. However, the properties and function of cholinergic and glutamatergic waves in ON- and OFF-SACs still remain poorly understood. In the present work, we performed whole-cell patch-clamp recordings and Ca2+ imaging from genetically labeled ON- and OFF-SACs in mouse flat-mount retinas. We found that both SAC subtypes exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves. Interestingly, ON-SACs had wave-induced action potentials (APs) in an age-dependent manner, but OFF-SACs did not. Simultaneous Ca2+ imaging and patch-clamp recordings demonstrated that, during a cholinergic wave, APs of an ON-SAC appeared to promote the dendritic release of acetylcholine onto neighboring ON- and OFF-SACs, which enhances their Ca2+ transients. These results advance the understanding of the cellular mechanisms underlying correlated spontaneous activity in the developing retina.


Function ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Annette C Dolphin

Abstract Voltage-gated calcium channels are the principal conduits for depolarization-mediated Ca2+ entry into excitable cells. In this review, the biophysical properties of the relevant members of this family of channels, those that are present in presynaptic terminals, will be discussed in relation to their function in mediating neurotransmitter release. Voltage-gated calcium channels have properties that ensure they are specialized for particular roles, for example, differences in their activation voltage threshold, their various kinetic properties, and their voltage-dependence of inactivation. All these attributes play into the ability of the various voltage-gated calcium channels to participate in different patterns of presynaptic vesicular release. These include synaptic transmission resulting from single action potentials, and longer-term changes mediated by bursts or trains of action potentials, as well as release resulting from graded changes in membrane potential in specialized sensory synapses.


2015 ◽  
Vol 112 (48) ◽  
pp. 14954-14959 ◽  
Author(s):  
Calvin Zhang ◽  
Charles S. Peskin

The probabilistic nature of neurotransmitter release in synapses is believed to be one of the most significant sources of noise in the central nervous system. We show how p0, the probability of release per docked vesicle when an action potential arrives, affects the dynamics of the rate of vesicle release in response to changes in the rate of arrival of action potentials. Furthermore, we examine the theoretical capability of a synapse in the estimation of desired signals using information from the stochastic vesicle release events under the framework of optimal linear filter theory. We find that a small p0, such as 0.1, reduces the error in the reconstruction of the input, or in the reconstruction of the time derivative of the input, from the time series of vesicle release events. Our results imply that the probabilistic nature of synaptic vesicle release plays a direct functional role in synaptic transmission.


1999 ◽  
Vol 81 (3) ◽  
pp. 1318-1329 ◽  
Author(s):  
Jesper Tegnér ◽  
Sten Grillner

Interactive effects of the GABABergic modulation of calcium channels and calcium-dependent potassium channels in lamprey. The GABAB-mediated modulation of spinal neurons in the lamprey is investigated in this study. Activation of GABAB receptors reduces calcium currents through both low- (LVA) and high-voltage activated (HVA) calcium channels, which subsequently results in the reduction of the calcium-dependent potassium (KCa) current. This in turn will reduce the peak amplitude of the afterhyperpolarization (AHP). We used the modulatory effects of GABAB receptor activation on N-methyl-d-aspartate (NMDA)-induced, TTX-resistant membrane potential oscillations as an experimental model in which to separate the effects of GABAB receptor activation on LVA calcium channels from that on KCachannels. We show experimentally and by using simulations that a direct effect on LVA calcium channels can account for the effects of GABAB receptor activation on intrinsic membrane potential oscillations to a larger extent than indirect effects mediated via KCa channels. Furthermore, by conducting experiments and simulations on intrinsic membrane potential oscillations, we find that KCa channels may be activated by calcium entering through LVA calcium channels, providing that the decay kinetics of the calcium that enters through LVA calcium channels is not as slow as the calcium entering via NMDA receptors. A combined experimental and computational analysis revealed that the LVA calcium current also contributes to neuronal firing properties.


1993 ◽  
Vol 70 (1) ◽  
pp. 284-298 ◽  
Author(s):  
K. Bielefeldt ◽  
M. B. Jackson

1. The contribution of a calcium-activated potassium channel to action-potential failure was studied in nerve terminals of the rat posterior pituitary. 2. Depolarizing current injections under current clamp were faithfully followed by action potentials for stimulation frequencies of < or = 12 Hz. Further increases in frequency resulted in action-potential failure within a few hundred milliseconds. The fraction of failures increased with stimulation frequency. This decrease in excitability was concomitant with a hyperpolarization from -57.3 +/- 1.4 to -61.3 +/- 1.4 (SE) mV. 3. The decrease in excitability was dependent on calcium influx through voltage-dependent calcium channels, because action-potential failures did not occur at frequencies < or = 30 Hz in the presence of cadmium. The dihydropyridine agonist BayK 8644 increased the fraction of failed action potentials. 4. Depolarizations from -80 to 10 mV for 3 s evoked macroscopic potassium currents with a rapidly activated, transient component and a slowly developing, noninactivating component. The late outward current was dependent on calcium influx, because it was reduced by cadmium and enhanced by BayK 8644. 5. Tetraethylammonium and 4-aminopyridine effectively blocked potassium outward currents but failed to distinguish this calcium-dependent potassium channel from the other two potassium channels in this preparation. Charybdotoxin and apamin did not affect potassium currents in this preparation. 6. In excised inside-out patches, the calcium-dependent potassium channel had a slope conductance of 193 pS. The open probability changed e-fold per 14.8 mV change in membrane potential with a calcium concentration at the cytoplasmic membrane face ([Ca]i) of 100 nM. 7. The channel was highly sensitive to [Ca]i. Depolarizations to 100 mV at 10 nM [Ca]i activated the channel half-maximally. When [Ca]i was raised to 250 nM, the voltage for half-maximal activation shifted to -16 mV. Calcium also decreased the steepness of the voltage activation curve. 8. At a constant membrane potential, pressure ejection of calcium to the cytosolic face of an excised patch activated the channel with a delay of 82 ms. This slow activation in excised patches was consistent with the slow activation of the delayed component of the macroscopic current. 9. At constant calcium concentration, the time course of activation exhibited a strong voltage dependence. Most of the channels did not inactivate during depolarizations lasting < or = 300 ms. 10. The channel exhibited complex gating, with at least two distinct open and closed states.(ABSTRACT TRUNCATED AT 400 WORDS)


2020 ◽  
Author(s):  
Rong-Shan Yan ◽  
Xiong-Li Yang ◽  
Yong-Mei Zhong ◽  
Dao-Qi Zhang

AbstractCorrelated spontaneous activity in the developing retina (termed “retinal waves”) plays an instructive role in refining neural circuits of the visual system. Depolarizing (ON) and hyperpolarizing (OFF) starburst amacrine cells (SACs) initiate and propagate cholinergic retinal waves. Where cholinergic retinal waves stop, SACs are thought to be driven by glutamatergic retinal waves initiated by ON-bipolar cells. However, the properties and function of cholinergic and glutamatergic waves in ON- and OFF-SACs still remain poorly understood. As expected, we found that both SAC subtypes exhibited spontaneous rhythmic depolarization during cholinergic and glutamatergic waves. Interestingly, ON-SACs had wave-induced action potentials (APs) in an age-dependent manner, but OFF-SACs did not. We further found that the number of APs in ON-SACs was correlated with the amplitude of Ca2+ transients of either ON- or OFF-SACs during cholinergic retinal waves. These results advance the understanding of the cellular mechanisms underlying correlated spontaneous activity in the developing retina.


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