scholarly journals Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission

2011 ◽  
Vol 106 (2) ◽  
pp. 680-689 ◽  
Author(s):  
Colin G. Evans ◽  
Bjoern Ch. Ludwar ◽  
Timothy Kang ◽  
Elizabeth C. Cropper
Keyword(s):  
Membrane Potential ◽  
Synaptic Transmission ◽  
Electrical Coupling ◽  
Mammalian Brain ◽  
Resting Membrane Potential ◽  
Presynaptic Membrane ◽  
Electrical Transmission ◽  
A Cell ◽  
Peripheral Activation ◽  
Chemical Transmission

The growing realization that electrical coupling is present in the mammalian brain has sparked renewed interest in determining its functional significance and contrasting it with chemical transmission. One question of interest is whether the two types of transmission can be selectively regulated, e.g., if a cell makes both types of connections can electrical transmission occur in the absence of chemical transmission? We explore this issue in an experimentally advantageous preparation. B21, the neuron we study, is an Aplysia sensory neuron involved in feeding that makes electrical and chemical connections with other identified cells. Previously we demonstrated that chemical synaptic transmission is membrane potential dependent. It occurs when B21 is centrally depolarized prior to and during peripheral activation, but does not occur if B21 is peripherally activated at its resting membrane potential. In this article we study effects of membrane potential on electrical transmission. We demonstrate that maximal potentiation occurs in different voltage ranges for the two types of transmission, with potentiation of electrical transmission occurring at more hyperpolarized potentials (i.e., requiring less central depolarization). Furthermore, we describe a physiologically relevant type of stimulus that induces both spiking and an envelope of depolarization in the somatic region of B21. This depolarization does not induce functional chemical synaptic transmission but is comparable to the depolarization needed to maximally potentiate electrical transmission. In this study we therefore characterize a situation in which electrical and chemical transmission can be selectively controlled by membrane potential.

Steps in the development of chemical and electrical synapses by pairs of identified leech neurons in culture

1989 ◽  
Vol 236 (1284) ◽  
pp. 253-268 ◽  
Keyword(s):  
Synaptic Transmission ◽  
Electrical Coupling ◽  
The Other ◽  
Enzyme Treatment ◽  
Sensory Cells ◽  
Electrical Transmission ◽  
Retzius Cells ◽  
Chemical Synapses ◽  
P Cells ◽  
Chemical Transmission

Experiments have been made to follow the development of chemical and electrical transmission between pairs of leech neurons in culture. 1. The cell bodies of identified neurons were isolated from the CNS by suction after mild enzyme treatment, together with a length of the initial segment (or ‘stump’). The neurons tested were Retzius cells (R), annulus erector motoneurons (AE), Anterior pagoda cells (AP) and pressure sensory cells (P). Pairs of cells were placed together in various configurations, with different sites on their surfaces making contact. 2. When pairs of Retzius cells were apposed with their stumps touching, serotonergic, chemically mediated synaptic transmission became apparent before electrical transmission. By 2.5 h impulses in either of the two Retzius cells produced hyperpolarizing inhibitory potentials in the other. These potentials were reversed by raised intracellular CI and showed clear facilitation. The strength of chemical transmission between Retzius cells increased over the next 72 h. 3. After chemical transmission had been established, weak non-recti­fying electrical transmission became apparent between Retzius cells at about 24–72 h. By 4 days coupling became stronger and tended to obscure chemically evoked synaptic potentials. 4. When pairs of Retzius cells were aligned in culture with the tip of one cell stump touching the soma of the other, chemical transmission also developed rapidly. Transmission was, however, in one direction, from stump to soma. At later stages non-rectifying electrical coupling devel­oped as with stump-stump configuration. With the cell bodies of two Retzius cells apposed, electrical coupling developed after several days, before chemical transmission could be observed. 5. When Retzius and P cells were cultured with their stumps in con­tact, inhibitory chemical synaptic transmission developed within 24 h. Transmission was always in one direction, from Retzius to P cell. Electrical coupling of Retzius and P cells never occurred whatever the spatial relations of the cells to one another. 6. Annulus erector motoneurons, which contain ACh and a peptide resembling FMRFamide, first developed electrical coupling when the two stumps were in contact and then, later, bi-directional chemical transmission. Anterior Pagoda pairs placed stump-to-stump showed electrical connections. 7. Electronmicrographs revealed the presence of synaptic structures within24 h after Retzius-Retzius, Retzius-P or AE–AE stumps were apposed. 8. The specificity of connections between cultured cells was similar to that observed in earlier experiments. A marked difference was in the speed and reliability with which chemical synapses developed when stumps were in contact. The results show that the tip of a neuron represents a preferential site for the formation of chemical synapses.

scholarly journals A High-Throughput Electrophysiology Assay Identifies Inhibitors of the Inwardly Rectifying Potassium Channel Kir7.1

2015 ◽  
Vol 20 (6) ◽  
pp. 739-747 ◽  
Author(s):  
Paul D. Wright ◽  
Srinivasan Kanumilli ◽  
David Tickle ◽  
Jamie Cartland ◽  
Nathalie Bouloc ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potassium Channel ◽  
Screening Strategy ◽  
Resting Membrane Potential ◽  
Pharmacological Characterization ◽  
Inwardly Rectifying Potassium Channel ◽  
A Cell ◽  
Automated Patch Clamp ◽  
Patch Clamp Electrophysiology ◽  
Inwardly Rectifying

Kir7.1 is an inwardly rectifying potassium channel that has been implicated in controlling the resting membrane potential of the myometrium. Abnormal uterine activity in pregnancy plays an important role in postpartum hemorrhage, and novel therapies for this condition may lie in manipulation of membrane potential. This work presents an assay development and screening strategy for identifying novel inhibitors of Kir7.1. A cell-based automated patch-clamp electrophysiology assay was developed using the IonWorks Quattro (Molecular Devices, Sunnyvale, CA) system, and the iterative optimization is described. In total, 7087 compounds were tested, with a hit rate (>40% inhibition) of 3.09%. During screening, average Z′ values of 0.63 ± 0.09 were observed. After chemistry triage, lead compounds were resynthesized and activity confirmed by IC50 determinations. The most potent compound identified (MRT00200769) gave rise to an IC50 of 1.3 µM at Kir7.1. Compounds were assessed for selectivity using the inwardly rectifying potassium channel Kir1.1 (ROMK) and hERG (human Ether-à-go-go Related Gene). Pharmacological characterization of known Kir7.1 inhibitors was also carried out and analogues of VU590 tested to assess selectivity at Kir7.1.

scholarly journals Response to coincident inputs in electrically coupled primary afferents is heterogeneous and is enhanced by H-current (IH) modulation

2019 ◽  
Vol 122 (1) ◽  
pp. 151-175
Author(s):  
Federico Davoine ◽  
Sebastian Curti
Keyword(s):  
Neuronal Excitability ◽  
Signal To Noise Ratio ◽  
Electrical Coupling ◽  
Primary Afferents ◽  
Coincidence Detection ◽  
Mammalian Brain ◽  
Electrical Transmission ◽  
Electrical Synapses ◽  
Electrophysiological Properties ◽  
Cationic Current

Electrical synapses represent a widespread modality of interneuronal communication in the mammalian brain. These contacts, by lowering the effectiveness of random or temporally uncorrelated inputs, endow circuits of coupled neurons with the ability to selectively respond to simultaneous depolarizations. This mechanism may support coincidence detection, a property involved in sensory perception, organization of motor outputs, and improvement signal-to-noise ratio. While the role of electrical coupling is well established, little is known about the contribution of the cellular excitability and its modulations to the susceptibility of groups of neurons to coincident inputs. Here, we obtained dual whole cell patch-clamp recordings of pairs of mesencephalic trigeminal (MesV) neurons in brainstem slices from rats to evaluate coincidence detection and its determinants. MesV neurons are primary afferents involved in the organization of orofacial behaviors whose cell bodies are electrically coupled mainly in pairs through soma-somatic gap junctions. We found that coincidence detection is highly heterogeneous across the population of coupled neurons. Furthermore, combined electrophysiological and modeling approaches reveal that this heterogeneity arises from the diversity of MesV neuron intrinsic excitability. Consistently, increasing these cells’ excitability by upregulating the hyperpolarization-activated cationic current ( IH) triggered by cGMP results in a dramatic enhancement of the susceptibility of coupled neurons to coincident inputs. In conclusion, the ability of coupled neurons to detect coincident inputs is critically shaped by their intrinsic electrophysiological properties, emphasizing the relevance of neuronal excitability for the many functional operations supported by electrical transmission in mammals. NEW & NOTEWORTHY We show that the susceptibility of pairs of coupled mesencephalic trigeminal (MesV) neurons to coincident inputs is highly heterogenous and depends on the interaction between electrical coupling and neuronal excitability. Additionally, upregulating the hyperpolarization-activated cationic current ( IH) by cGMP results in a dramatic increase of this susceptibility. The IH and electrical synapses have been shown to coexist in many neuronal populations, suggesting that modulation of this conductance could represent a common strategy to regulate circuit operation supported by electrical coupling.

Depression of glutamate-mediated synaptic transmission by benzyl alcohol

1977 ◽  
Vol 55 (4) ◽  
pp. 917-922 ◽  
Author(s):  
Carol A. Colton ◽  
Joel S. Colton
Keyword(s):  
Membrane Potential ◽  
Neuromuscular Junction ◽  
Synaptic Transmission ◽  
Benzyl Alcohol ◽  
Reversal Potential ◽  
Membrane Resistance ◽  
Postsynaptic Membrane ◽  
Resting Membrane Potential ◽  
End Plate ◽  
Potential Frequency

The data obtained from this study suggest that the nonionizable anesthetic benzyl alcohol has two prominent actions on GABA- and glutamate-mediated synaptic transmission at the lobster neuromuscular junction. They are as follows: (1) depression of the excitatory end-plate potential and the postsynaptic membrane response to applied glutamate, and (2) a hyperpolarization of the postsynaptic resting membrane potential associated with a decrease in effective membrane resistance. No change in amplitude of the inhibitory end-plate potential or inhibitory reversal potential was seen. Excitatory miniature end-plate potential frequency was also unaffected. The depression of excitatory synaptic transmission appears to be due to a decreased responsiveness of the postsynaptic receptor–ionophore complex.

Potassium channel dysfunction and depolarized resting membrane potential in a cell model of SCA3

2006 ◽  
Vol 201 (1) ◽  
pp. 182-192 ◽  
Author(s):  
Monika Jeub ◽  
Martin Herbst ◽  
Alexander Spauschus ◽  
Henrik Fleischer ◽  
Thomas Klockgether ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potassium Channel ◽  
Cell Model ◽  
Resting Membrane Potential ◽  
A Cell

scholarly journals Electrical Transmission among Neurons in the Buccal Ganglion of a Mollusc, Navanax inermis

1970 ◽  
Vol 55 (4) ◽  
pp. 484-496 ◽  
Author(s):  
H. Levitan ◽  
L. Tauc ◽  
J. P. Segundo
Keyword(s):  
Membrane Potential ◽  
Current Flow ◽  
Electrical Coupling ◽  
Relative Size ◽  
Sudden Expansion ◽  
Minor Role ◽  
Common Source ◽  
Coupling Coefficients ◽  
Electrical Transmission ◽  
Buccal Ganglion

The opisthobranch mollusc, Navanax, is carnivorous and cannibalistic. Prey are swallowed whole by way of a sudden expansion of the pharynx. The buccal ganglion which controls this sucking action was isolated and bathed in seawater. Attention was focused upon 10 identifiable cells visible on the ganglion's rostral side. Two cells were observed simultaneously, and each was penetrated with two glass microelectrodes, one for polarizing the membrane and the other for recording membrane potential variations. The coupling coefficients for direct current flow and action potentials of several identified cells were tabulated. Attenuation was essentially independent of the direction of current flow, but depended upon the relative size of the directly and indirectly polarized cells. The attenuation of subthreshold sinusoidally varying voltages increased with frequency above about 1 Hz. The coupling coefficient for spikes was lower than for DC due to greater high frequency attenuation. There is considerable similarity in the spontaneous PSP's of all cells, which is not due to the electrical coupling but to input from a common source. The 10 cells were not chemically interconnected but some were electrically connected to interneurons which fed back chemically mediated PSP's. The feedback can be negative or positive depending upon the membrane potential of the postsynaptic cell. We conclude that electrical coupling among the 10 cells plays a minor role in sudden pharyngeal contractions but that the dual electrical-chemical coupling with interneurons may be important in this respect.

Effect of low chloride on relaxation in hamster diaphragm muscle

1986 ◽  
Vol 61 (1) ◽  
pp. 180-184 ◽  
Author(s):  
S. A. Esau ◽  
N. Sperelakis
Keyword(s):  
Membrane Potential ◽  
Muscle Fatigue ◽  
Time Constant ◽  
Diaphragm Muscle ◽  
Resting Membrane Potential ◽  
Krebs Solution ◽  
Sarcolemmal Membrane ◽  
Cl Conductance

With muscle fatigue the chloride (Cl-) conductance of the sarcolemmal membrane decreases. The role of lowered Cl- conductance in the prolongation of relaxation seen with fatigue was studied in isolated hamster diaphragm strips. The muscles were studied in either a Krebs solution or a low Cl- solution in which half of the NaCl was replaced by Na-gluconate. Short tetanic contractions were produced by a 160-ms train of 0.2-ms pulses at 60 Hz from which tension (T) and the time constant of relaxation were measured. Resting membrane potential (Em) was measured using KCl-filled microelectrodes with resistances of 15–20 M omega. Mild fatigue (20% fall in tension) was induced by 24–25 tetanic contractions at the rate of 2/s. There was no difference in Em or T in the two solutions, either initially or with fatigue. The time constant of relaxation was greater in low Cl- solution, both initially (22 +/- 3 vs. 18 +/- 5 ms, mean +/- SD, P less than 0.05) and with fatigue (51 +/- 18 vs. 26 +/- 7 ms, P less than 0.005). Lowering of sarcolemmal membrane Cl- conductance appears to play a role in the slowing of relaxation of hamster diaphragm muscle seen with fatigue.

Calcium channels and excitation–contraction coupling in cardiac cells. I. Two components of contraction in guinea-pig papillary muscle

1987 ◽  
Vol 65 (9) ◽  
pp. 1821-1831 ◽  
Author(s):  
E. Honoré ◽  
M. M. Adamantidis ◽  
B. A. Dupuis ◽  
C. E. Challice ◽  
P. Guilbault
Keyword(s):  
Membrane Potential ◽  
Guinea Pig ◽  
Papillary Muscle ◽  
Cardiac Cells ◽  
Resting Membrane Potential ◽  
Tonic Component ◽  
Contraction Coupling ◽  
Rich Solution ◽  
The Relationship ◽  
Guinea Pig Atria

Biphasic contractions have been obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) containing 0.3 μM isoproterenol; whereas in guinea-pig atria, the same conditions led to monophasic contractions corresponding to the first component of contraction in papillary muscle. The relationships between the amplitude of the two components of the biphasic contraction and the resting membrane potential were sigmoidal curves. The first component of contraction was inactivated for membrane potentials less positive than those for the second component. In Na+-low solution (25 mM), biphasic contraction became monophasic subsequent to the loss of the second component, but tetraethylammonium unmasked the second component of contraction. The relationship between the amplitude of the first component of contraction and the logarithm of extracellular Ca2+ concentration was complex, whereas for the second component it was linear. When Ca2+ ions were replaced by Sr2+ ions, only the second component of contraction was observed. It is suggested that the first component of contraction may be triggered by a Ca2+ release from sarcoplasmic reticulum, induced by the fast inward Ca2+ current and (or) by the depolarization. The second component of contraction may be due to a direct activation of contractile proteins by Ca2+ entering the cell along with the slow inward Ca2+ current and diffusing through the sarcoplasm. These results do not exclude the existence of a third "tonic" component, which could possibly be mixed with the second component of contraction.

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