Ionic Channels

1998 ◽  
Author(s):  
Christof Koch
Keyword(s):  
Membrane Potential ◽  
Giant Axon ◽  
Ionic Channels ◽  
Na Channel ◽  
Full Account ◽  
Ionic Fluxes ◽  
Synaptic Receptors ◽  
The Central Nervous System ◽  
Action Potential Initiation ◽  
Electrical Signaling

In the previous chapters, we studied the spread of the membrane potential in passive or active neuronal structures and the interaction among two or more synaptic inputs. We have yet to give a full account of ionic channels, the elementary units underlying all of this dizzying variety of electrical signaling both within and between neurons. Ionic channels are individual proteins anchored within the bilipid membrane of neurons, glia, or other cells, and can be thought of as water-filled macromolecular pores that are permeable to particular ions. They can be exquisitely voltage sensitive, as the fast sodium channel responsible for the sodium spike in the squid giant axon, or they can be relatively independent of voltage but dependent on the binding of some neurotransmitter, as is the case for most synaptic receptors, such as the acetylcholine receptor at the vertebrate neuromuscular junction or the AMPA and GABA synaptic receptors mediating excitation and inhibition in the central nervous system. Ionic channels are ubiquitous and provide the substratum for all biophysical phenomena underlying information processing, including mediating synaptic transmission, determining the membrane voltage, supporting action potential initiation and propagation, and, ultimately, linking changes in the membrane potential to effective output, such as the secretion of a neurotransmitter or hormone or the contraction of a muscle fiber. Individual ionic channels are amazingly specific. A typical potassium channel can distinguish a K+ ion with a 1.33 Å radius from a Na+ ion of 0.95 Å radius, selecting the former over the latter by a factor of 10,000. This single protein can do this selection at a rate of up to 100 million ions each second (Doyle et al, 1998). At the time of Hodgkin and Huxley’s seminal study in the early 1950s, two broad classes of transport mechanisms were competing as plausible ways for carrying ionic fluxes across the membrane: carrier molecules and pores. At the time, no direct evidence for either one existed. It was not until the early 1970s that the fast ACh synaptic receptor and the Na channel were chemically isolated and purified and identified as proteins.

Brain stem – from general view to computational model based on switchboard rules of operation

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Włodzisław Duch ◽  
Dariusz Mikołajewski
Keyword(s):  
Brain Stem ◽  
Large Scale ◽  
Ionic Channels ◽  
General View ◽  
The Central Nervous System ◽  
Network States ◽  
Large Scale Simulations ◽  
Influence Of Noise ◽  
The Brain ◽  
Sufficient Precision

Abstract Despite great progress in understanding the functions and structures of the central nervous system (CNS) the brain stem remains one of the least understood systems. We know that the brain stem acts as a decision station preparing the organism to act in a specific way, but such functions are rather difficult to model with sufficient precision to replicate experimental data due to the scarcity of data and complexity of large-scale simulations of brain stem structures. The approach proposed in this article retains some ideas of previous models, and provides more precise computational realization that enables qualitative interpretation of the functions played by different network states. Simulations are aimed primarily at the investigation of general switching mechanisms which may be executed in brain stem neural networks, as far as studying how the aforementioned mechanisms depend on basic neural network features: basic ionic channels, accommodation, and the influence of noise.

Insulin release, cGMP, cAMP, and membrane potential in acetylcholine-stimulated islets.

1978 ◽  
Vol 235 (5) ◽  
pp. E493 ◽  
Author(s):  
E Gagerman ◽  
L A Idahl ◽  
H P Meissner ◽  
I B T�ljedal
Keyword(s):  
Membrane Potential ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Cyclic Gmp ◽  
Spike Activity ◽  
Obvious Effect ◽  
Ionic Fluxes ◽  
Mouse Islets ◽  
Silent State ◽  
Esterase Inhibitor

Acetylcholine potentiated the glucose-induced insulin release from microdissected mouse islets of Langerhans but had no effect on basal insulin release. Significant potentiation was obtained with 0.1 micron acetylcholine in the presence of 10 micron eserine and with 1 micron or more acetylcholine in the absence of a choline esterase inhibitor. Carbamylcholine, too, potentiated insulin release. Potentiation was blocked by methylatropine, whereas methylatropine alone had no effect on insulin release. Acetylcholine or carbamylcholine (5-500 micron) had no obvious effect on cyclic GMP or cyclic AMP in the islets. In the presence of 11.1 mM D-glucose, the membrane potential of beta-cells oscillated slowly between a polarized silent state of -50 to -55 mV and a depolarized active state of -33 to -39 mV, at which a fast spike activity occurred. Acetylcholine made the potential stay at the plateau and induced a continuous spike activity pattern. Atropine inhibited the electrical effects of acetylcholine but not those of glucose alone. It is suggested that cholinergic potentiation of insulin release is mediated by changes of transmembrane ionic fluxes, probably without the intervention of cyclic GMP or cyclic AMP.

Propagation of electrical signals along giant nerve fibres

1952 ◽  
Vol 140 (899) ◽  
pp. 177-183 ◽  
Keyword(s):  
Sea Water ◽  
Giant Axon ◽  
High Concentration ◽  
Nerve Fibres ◽  
Giant Fibre ◽  
Electrical Signals ◽  
Small Fibre ◽  
The Central Nervous System ◽  
Good Conductor ◽  
Ionic Movement

In this part of the discussion we shall attempt to describe the way in which electrical signals are propagated along the giant nerve fibres of squids and cuttlefish. These fibres consist of cylinders of protoplasm, 0.2 to 0.6 mm in diameter, and ire bounded by a thin membrane which acts as a barrier to ionic movement. The protoplasm, or axoplasm as it is commonly called, is an aqueous gel which is a reasonably good conductor of electricity. It contains a high concentration of K + and a low concentration of Na + and Cl - , this situation being the reverse of that in the animal’s blood or sea water. Axons which are left in sea water slowly lose potassium and gain sodium. This process takes about 24 hours and is roughly 80 000 times slower than the diffusion of ions out of a cylinder of gelatin of the same size. The interchange of sodium and potassium is very greatly accelerated by stimulating the fibres. Experiments with tracers, such as those made by Keynes & Lewis (1951) or Rothenberg (1950), allow the interchange to be measured quantitatively, and there is general agreement that the impulse is associated with an entry of 3 to 4 µ µ mol of Na + through 1 cm 2 of membrane and an exit of a corresponding quantity of K + . These quantities are very small compared with the total number of ions inside the fibre. In the giant axon of the squid the quantity of potassium lost in each impulse corresponds to only about 1 millionth if the total internal potassium. One would therefore expect that a giant fibre should be able to carry a great many impulses without recharging its batteries by metabolism. On the other hand, a very small fibre such as a dendrite in the central nervous system should be much more dependent on metabolism since the ratio of surface to volume may be nearly 1000 times greater.

Ionic channels in corneal endothelium

1996 ◽  
Vol 270 (4) ◽  
pp. C975-C989 ◽  
Author(s):  
J. L. Rae ◽  
M. A. Watsky
Keyword(s):  
Patch Clamp ◽  
Corneal Endothelium ◽  
Single Channel ◽  
Cell Voltage ◽  
Anion Channel ◽  
Ionic Channels ◽  
K Channel ◽  
Na Channel ◽  
Channel Blockers ◽  
K Currents

Single-channel patch-clamp techniques as well as standard and perforated-patch whole cell voltage-clamp techniques have been applied to the study of ionic channels in the corneal endothelium of several species. These studies have revealed two major K+ currents. One is due to an anion- and temperature-stimulated channel that is blocked by Cs+ but not by most other K+ channel blockers, and the other is similar to the family of A-currents found in excitable cells. The A-current is transient after a depolarizing voltage step and is blocked by both 4-aminopyridine and quinidine. These two currents are probably responsible for setting the -50 to -60 mV resting voltage reported for these cells. A Ca(2+)-activated ATP-inhibited nonselective cation channel and a tetrodotoxin-blocked Na+ channel are possible Na+ inflow pathways, but, given their gating properties, it is not certain that either channel works under physiological conditions. A large-conductance anion channel has also been identified by single-channel patch-clamp techniques. Single corneal endothelial cells have input resistances of 5-10 G omega and have steady-state K+ currents that are approximately 10 pA at the resting voltage. Pairs or monolayers of cells are electrically coupled and dye coupled through gap junctions.

scholarly journals Relative Ion Permeabilities in the Crayfish Giant Axon Determined from Rapid External Ion Changes

1967 ◽  
Vol 50 (7) ◽  
pp. 1929-1953 ◽  
Author(s):  
Alfred Strickholm ◽  
B. Gunnar Wallin
Keyword(s):  
Membrane Potential ◽  
Potassium Level ◽  
Potassium Concentration ◽  
Giant Axon ◽  
Resting Potential ◽  
Resting Membrane Potential ◽  
Constant Field ◽  
Appreciable Effect ◽  
Ion Concentrations ◽  
External Potassium

The changes in membrane potential of isolated, single crayfish giant axons following rapid shifts in external ion concentrations have been studied. At normal resting potential the immediate change in membrane potential after a variation in external potassium concentration is quite marked compared to the effect of an equivalent chloride change. If the membrane is depolarized by a maintained potassium elevation, the immediate potential change due to a chloride variation becomes comparable to that of an equivalent potassium change. There is no appreciable effect on membrane potential when external sodium is varied, at normal or at a depolarized membrane potential. Starting from the constant field equation, expressions for the permeability ratios PCl/PK, PNa/PK, and for intracellular potassium and chloride concentrations are derived. At normal resting membrane potential, PCl/PK is 0.13 but at a membrane potential of -53 mv (external potassium level increased about five times) it is 0.85. The intracellular concentrations of potassium and chloride are estimated to be 233 and 34 mM, respectively, and it is pointed out that this is not compatible with ions distributed in a Nernst equilibrium across the membrane. It is also stressed that the information given by a plot of membrane potential vs. the logarithm of external potassium concentrations is very limited and rests upon several important assumptions.

Molecular basis for pore blockade of human Na+ channel Nav1.2 by the μ-conotoxin KIIIA

Science ◽  
2019 ◽  
Vol 363 (6433) ◽  
pp. 1309-1313 ◽  
Author(s):  
Xiaojing Pan ◽  
Zhangqiang Li ◽  
Xiaoshuang Huang ◽  
Gaoxingyu Huang ◽  
Shuai Gao ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Rational Design ◽  
Na Channel ◽  
Auxiliary Subunit ◽  
Cryo Electron Microscopy ◽  
Initiation And Propagation ◽  
The Central Nervous System ◽  
Immunoglobulin Domain ◽  
Pore Domain ◽  
Pore Blocker

The voltage-gated sodium channel Nav1.2 is responsible for the initiation and propagation of action potentials in the central nervous system. We report the cryo–electron microscopy structure of human Nav1.2 bound to a peptidic pore blocker, the μ-conotoxin KIIIA, in the presence of an auxiliary subunit, β2, to an overall resolution of 3.0 angstroms. The immunoglobulin domain of β2 interacts with the shoulder of the pore domain through a disulfide bond. The 16-residue KIIIA interacts with the extracellular segments in repeats I to III, placing Lys7 at the entrance to the selectivity filter. Many interacting residues are specific to Nav1.2, revealing a molecular basis for KIIIA specificity. The structure establishes a framework for the rational design of subtype-specific blockers for Nav channels.

scholarly journals Grayanotoxin, veratrine, and tetrodotoxin-sensitive sodium pathways in the Schwann cell membrane of squid nerve fibers.

1976 ◽  
Vol 67 (3) ◽  
pp. 369-380 ◽  
Author(s):  
J Villegas ◽  
C Sevcik ◽  
F V Barnola ◽  
R Villegas
Keyword(s):  
Membrane Potential ◽  
Cell Membrane ◽  
Schwann Cell ◽  
Nerve Fiber ◽  
Schwann Cells ◽  
Giant Axon ◽  
Nerve Fibers ◽  
Resting Membrane Potential ◽  
External Application ◽  
Axon Membrane

The actions of grayanotoxin I, veratrine, and tetrodotoxin on the membrane potential of the Schwann cell were studied in the giant nerve fiber of the squid Sepioteuthis sepioidea. Schwann cells of intact nerve fibers and Schwann cells attached to axons cut lengthwise over several millimeters were utilized. The axon membrane potential in the intact nerve fibers was also monitored. The effects of grayanotoxin I and veratrine on the membrane potential of the Schwann cell were found to be similar to those they produce on the resting membrane potential of the giant axon. Thus, grayanotoxin I (1-30 muM) and veratrine (5-50 mug-jl-1), externally applied to the intact nerve fiber or to axon-free nerve fiber sheaths, produce a Schwann cell depolarization which can be reversed by decreasing the external sodium concentration or by external application of tetrodotoxin. The magnitude of these membrane potential changes is related to the concentrations of the drugs in the external medium. These results indicate the existence of sodium pathways in the electrically unexcitable Schwann cell membrane of S. sepioidea, which can be opened up by grayanotoxin I and veratrine, and afterwards are blocked by tetrodotoxin. The sodium pathways of the Schwann cell membrane appear to be different from those of the axolemma which show a voltage-dependent conductance.

scholarly journals Membrane Potentials of the Lobster Giant Axon Obtained by Use of the Sucrose-Gap Technique

1962 ◽  
Vol 45 (6) ◽  
pp. 1195-1216 ◽  
Author(s):  
Fred J. Julian ◽  
John W. Moore ◽  
David E. Goldman
Keyword(s):  
Membrane Potential ◽  
Action Potential ◽  
Sea Water ◽  
Sucrose Solution ◽  
Chloride Concentration ◽  
Giant Axon ◽  
Membrane Resistance ◽  
Resting Potential ◽  
Gap Technique ◽  
Sucrose Gap

A method similar to the sucrose-gap technique introduced be Stäpfli is described for measuring membrane potential and current in singly lobster giant axons (diameter about 100 micra). The isotonic sucrose solution used to perfuse the gaps raises the external leakage resistance so that the recorded potential is only about 5 per cent less than the actual membrane potential. However, the resting potential of an axon in the sucrose-gap arrangement is increased 20 to 60 mv over that recorded by a conventional micropipette electrode when the entire axon is bathed in sea water. A complete explanation for this effect has not been discovered. The relation between resting potential and external potassium and sodium ion concentrations shows that potassium carries most of the current in a depolarized axon in the sucrose-gap arrangement, but that near the resting potential other ions make significant contributions. Lowering the external chloride concentration decreases the resting potential. Varying the concentration of the sucrose solution has little effect. A study of the impedance changes associated with the action potential shows that the membrane resistance decreases to a minimum at the peak of the spike and returns to near its initial value before repolarization is complete (a normal lobster giant axon action potential does not have an undershoot). Action potentials recorded simultaneously by the sucrose-gap technique and by micropipette electrodes are practically superposable.

scholarly journals Strophanthidin-sensitive sodium fluxes in metabolically poisoned frog skeletal muscle.

1976 ◽  
Vol 68 (4) ◽  
pp. 405-420 ◽  
Author(s):  
B G Kennedy ◽  
P De Weer
Keyword(s):  
Skeletal Muscle ◽  
Membrane Potential ◽  
Human Erythrocyte ◽  
Sodium Pump ◽  
Giant Axon ◽  
Squid Giant Axon ◽  
Frog Skeletal Muscle ◽  
Na Efflux ◽  
Unidirectional Fluxes ◽  
External K

Strophanthidin-sensitive and insensitive unidirectional fluxes of Na were measured in fog sartorius muscles whose internal Na levels were elevated by overnight storage in the cold. ATP levels were lowered, and ADP levels raised, by metabolic poisoning with either 2,4-dinitrofluorobenzene or iodoacetamide. Strophanthidin-sensitive Na efflux and influx both increased after poisoning, while strophanthidin-insensitives fluxes did not. The increase in efflux did not require the presence of external K but was greatly attenuated when Li replaced Na as the major external cation. Membrane potential was not markedly altered by 2,4-dinitrofluorobenzene. These observations indicate that the sodium pump of frog skeletal muscle resembles that of squid giant axon and human erythrocyte in its ability to catalyze Na-Na exchange to an extent determined by intracellular ATP/ADP levels.

scholarly journals Non-Linear Current-Potential Relations in an Axon Membrane

1961 ◽  
Vol 44 (6) ◽  
pp. 1055-1057 ◽  
Author(s):  
Kenneth S. Cole
Keyword(s):  
Membrane Potential ◽  
Giant Axon ◽  
Squid Giant Axon ◽  
External Current ◽  
Current Electrode ◽  
Axon Membrane ◽  
Linear Current ◽  
One Step ◽  
Original Derivation ◽  
Current Potential

The membrane current density, Im, in the squid giant axon has been calculated from the measured external current applied to the axon, Io, by the equation See PDF for Equation where Vm is the membrane potential under the current electrode and r1 and r2 are the external and internal longitudinal resistances. The original derivation of this equation included in one step an assumption of a linear relation between Im and Vm. It is shown that the same equation can be obtained without this restricting assumption.

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