Ion Channel Glossary

since officially joining the miller lab four days ago, i have been in ion channel literature hell. all i have been doing for the last four days is reading about the project i am going to be starting and all the necessary background. it really is interesting, but ~every four sentences i have to stop and look up the definition of a word.

it isn't like i am looking up 'dog' or 'pumpkin.' i have to look up words like 'constant field theory,' 'flicker,' or 'microiontopforesis' and i have come to find that these aren't your normal words. so i decided to be nice and put together a glossary for people so hopefully when they search for one of these obscure words they find this!

so anyways, here we go!



Access resistance: the electrical resistance between the inside of the patch pipette and the inside of the cell during a whole-cell recording. Compromises recordings by introducing a voltage-divider error and slowing the response time of the voltage clamp. Access resistance can be reduced by using larger patch pipettes and can be compensated electronically with the patch clamp amplifier.

Action Potential: the electrical signal, which rapidly propagates along the axon of nerve cells as well as over the surface of some muscle and glandular cells. It is the result of a change in membrane electrical potential, the underlying cause of which is a change in flow of ions across the membrane due to voltage-activated ion channels.

Activation: opening of a channel due to the presence of a gating signal.

Anion: a negatively charged particle.

Anomalous Mole-Fraction Dependence: where conductance or reversal potential goes thru a minimum or maximum as a function of the ratio of ionic concentrations. Calcium ion channels and Calcium-activated potassium channels are well-known examples of ion channels where this occurs.

Axon: highly specialized relatively long extension (process) of a neuron used for conduction of electrical messages (i.e. action potentials). Axons are considerably more specialized and therefore easier to understand than other excitable tissues. They contain the "bare minimum" of ion channels necessary for excitability. Larger vertebrate axons are insulated by myelin.

Block: when ion flow thru an ion channel is prohibited due to a physical obstruction within the pore; and can occur due to another ion, a drug or a toxin. Such molecules, which block ion flow, are known as "blocking agents". "Use-dependent block" or "phasic block" occurs when the drug (toxin, anesthetic, etc) blocks only the open form of the channel.

Cation: a positively charged particle.

Charge: the fundamental property of matter that is responsible for electrical phenomena. Charge (Q) is measured in Coulombs (C). Elementary charge, e = 1.602 x 10-19 Coulombs (C)

Conductance: refers to the rate of ion travel thru the channel and is often measured in siemens (S). Ions with high conductances are often said to have binding sites in the channel that are relatively high in free energy compared to an ion with lower conductance (which sticks more tightly to binding sites). Conductance is often designated as current divided by voltage, and since voltage is usually "clamped" in patch clamp experiments, relates directly to current of ions.

Conductivity: the ability of a substance to pass current. For a membrane, the conductivity (Gm) is measured in units of S/cm2 and G=Gm*area. For a cable (e.g. axon or dendrite), the conductivity (G,, for intracellular conductivity) is measured in units of S/cm and G=Gi*length/area (i.e. cross-sectional area).

Constant Field Theory: a theory to describe the permeabilities of membranes to ions. First put forth in the 1940s by Goldman (before ion channels were proven to exist in membranes), it attempts to describe ion movement in terms of simple diffusion thru water-filled "pores" in a membrane. Ions are assumed to move independently of one another and the channel properties. Also called the "independent electrodiffusion model", it has been successful in describing some aspects of ion permeabilities thru certain ion channels. The other major theory used to describe ion channel permeabilities is the "Rate Theory Model".

Current: the rate of charge movement. Current is measured in amperes (A), which is equivalent to coulombs per second (C/s). I = dQ/dt = Coulombs/sec = Amps (A).

Deactivation: closing of a channel due to removal of the gating signal (i.e. the opposite of activation).

Desensitization: closing of a ligand-gated channel despite the presence of a bound activating ligand. For example, glutamate receptors desensitize in the continued presence of glutamate.

Desolvation: where the ion is rehydrated when it moves outward from the ion channel pore into the bulk solution when it exits pore.

Dwell Times: can give information on kinetic processes. The amount of time a channel remains in the closed position. Also used to describe the amount of time an ion spends in an ion channel pore at a particular binding site.

Electro-osmosis: when ions forced to move thru a pore carry with them water molecules. Similar to streaming potential, but just the opposite.

Eyring rate theory: used to help explain what occurs when an ion traverses an ion channel pore. States that relative permeabilities relate to heights of energy barriers (which differ for different ions) and relative conductances relate to depths of the wells (i.e. ion binding sites) in the energy diagram.

Flicker: occurs when molecules other than the ion enter the channel opening and briefly blocks ion conductance. This can be seen on single-channel recordings as squiggly lines during the open time, as well as a lower overall conductance. "Desensitization" is believed to be due to too much ligand, for example acetylcholine and nAChR channels, blocking the channel rather than activating it. For CFTR, NPPB or DPC induces rapid flicker and therefore block pore.

Flux Coupling: a factor, which may reduce the ability of an ion to move thru a pore. It is due to the crowded conditions in the narrow part of the pore. When molecules diffuse within a restricted space, they lose their independence compared to the bulk solvent.

Flux-Ratio Criterion: an important test for whether or not ion channel pores can admit multiple ions at the same time. It was proposed by Ussing in 1949 and can be used to reveal flux coupling. A tracer ion is needed to measure the unidirectional flux across a membrane from both sides.

Gating: process by which ion channels open and close their pores. Some, such as voltage-gated ion channels, open and close depending on the electrical potential of the cell membrane. Others depend on such factors as cell volume, intracellular metabolic state (ATP concentration, etc), intracellular ligand and/or second messenger presence (Calcium, cyclic AMP due to light, etc), and extracellular ligands (neurotransmitters like acetylcholine, GABA). It always involves a change in the shape of the protein (called "allosterism").

Gating current: a current resulting when charged residues within an ion channel protein move through the electric field. In voltage-gated channels, a change in membrane potential causes the protein to move; this movement gives rise to the gating current.

Hodgkin-Huxley Model: developed by work with the squid giant axon, it was the first model to describe the ionic basis of excitation correctly. It had the effect of revolutionizing electrophysiology.

Inactivation: closing of a channel in the continued presence of the gating signal. The term "inactivation" is usually only applied to voltage-gated channels, whereas "desensitization" describes the analogous process for ligand-gated channels.

Kinetics: as applied to ion channels kinetics usually encompasses the study of rate of change ion channels undergo during gating, ion passage, etc. Kinetics is often used in order to uncover specific "mechanisms" channels undergo when changing from one state to another and to explain the phenomena of gating, "jumps", "bursts", "transition times", sub-conductance modes, ligand interactions, etc. Complex mathematical treatments involving the kinetics of ion channels have been undertaken in order to gain insight into how ion channels accomplish this.

Markov model: a probabilistic process over a finite set of states, often used to described channel behavior. Transitions between states are determined by rate constants. A zero-order Markov process has no memory; a first-order Markov process has a memory of one step, i.e., the possible states that a channel can occupy at time t depends on which state it was in at time t-1.

Membrane Potential: the inside potential minus the outside potential. The outside of the cell is often considered to be at ground potential (0 mV).

Microiontophoresis: where, during patch clamping of receptor ion channels such as nAChR, agonist is electrophoresed locally thru the microelectrode where it binds and activates the receptor.

Modulation: anything, which changes or modifies gating can cause "modulation". These can include ligand binding to the channel, post-translational modifications like phosphorylation, or changes in the process itself." Certain neurotransmitters such as GABA, serotonin, nitric oxide, and others can modulate ion channels indirectly by binding to other sites on cell membrane. They do this by influencing GPCRs. By changing the internal ion melieu of the cytoplasm, changes in the cell itself can take place. Fatty acids have been shown to bind directly to ion channels and modulate them.

Multi-Ion Pore: when an ion channel's pore is able to conduct more than one ion at a time. CFTR is believed to by one because of the presence of anomalous mole fraction effects in mixtures of chloride and SCN-.

Ohm's law: describes the relationship between voltage, current, and resistance, V=IR or R = V/I = Ohms (Ω); I = g V or g = I/V = Siemens (S).

Open State Probability (Po): the amount of time an ion channel is in the open configuration.

Permeability: describes how fast ions are able to move thru an ion channel (the rate of movement). The "depth" of the energy well for a particular ion generally determines it's permeability, or conductance. However, if an energy well is too deep, it can slow down the ion's rate of travel. Note: all binding sites for an ion in a channel have energy wells specific to the interaction that takes place.

Pore: part of ion channel, which forms path ions use to move from one side of membrane to other. Often lined with some hydrophilic amino acids. Sometimes filled with water. Pore lengths have been inferred for some ion channels by blocking the pore during conduction experiments using blocking agents with long spacer arms. CFTR's pore is estimated to be around 5.8A at its narrowest point. Narrow pores will necessitate removal of some or all of an ions hydration shell before allowing passage.

Potential Difference: the same as voltage. Another definition is the difference in potential energy experienced by a charged particle in two locations (the work required to move a charge from point A to B). Potential difference (E) is measured in volts (V). E = Joules/Coulomb = Volts (V).

Rate Theory Model: used to describe ion movement thru ion channels by considering ions not in terms of passive diffusion (i.e. electrodiffusion model) but as being able to bind to specific sites within the ion channel. The Rate Theory is an attempt to apply reaction rate theory developed by Eyring for enzymes to ion channels in hopes of gaining insight into particular mechanisms of ion conduction. The ultimate description of ion movement using this theory would involve use of "molecular dynamics simulations" in silico.

Rectification (of channels): characteristic of an ion channel, generally independent of gating, that biases the preferred direction of current flow to either the inward or outward direction. Rectification can be due to an intrinsic property of the channel or be conferred by voltage-dependent block by an extrinsic agent. For example, the relatively high concentration of K+ ions inside a cell can cause outward rectification of some K+ channels, because more K+ ions are available to carry outward current than the number available to carry inward current. This is called GHK rectification. Another type of rectification is caused by polyamines. These charged molecules are only present inside cells and at depolarized potentials they move into the pore of some voltage-gated and ligand-gated channels, thus limiting outward current (i.e. inward rectification). These factors cause the channel conductance to be voltage dependent, thus resulting in rectification.

Relative Conductance: when the conductance for a substitute ion relative to that of a standard ion is determined.

Relative Permeabilities: reflect the ability of an ion channel protein to pull an ion from solution into the "capture volume" within the pore vestibule. It may therefore be highly dependent on hydration energy. Some permeability sequences reflect low-affinity ion-pore interactions (ex: I>Br>Cl>F). The reverse sequence often indicates a high affinity interaction. CFTR has a more complex sequence, which indicates a combination of both low and high field strength interactions (Br>Cl>I>F). For most anions, the relative permeability is determined by the relative hydration energies of the ions.

Resistance: the inverse of conductance. That is, the ability of something to impede current. Resistance (R) is measured in Ohms (Ω).

Resistivity: the inverse of conductivity. Membrane resistivity (Rm) has units of resistivity (Ri) has units of Ωcm.

Reversal Potentials: often abbreviated E(rev). For CFTR (and other anion channels), it is the amount of negative membrane potential needed to be applied to reverse the flow of chloride when the concentration is at standard conditions. For CFTR this value is -30.31 mV. For example, if a particular anion requires a more negative E(rev) than for chloride then it may either permeate or conduct better than chloride depending on which is being determined, permeability (uses Goldman-Hodgkin-Katz equation) or conductance.

Selectivity: used to describe the variability in rate of movement of different ions thru the same ion channel. The "height" of the energy barrier of an ion channel's selectivity filter will help determine ion it let thru. Often, the term selectivity is not properly defined and can refer to either of the two processes of permeability or conduction. The distinction should always be made.

Selectivity Filter: a distinct part of an ion channel involved in selecting the type of ion it lets thru. First described by Hille in 1971, it is thought to be situated in the narrowest part of the pore, because this is the part of the channel where the protein and ion would presumably interact the most.

Siemens: a measurement of current conductance (often abbreviated "G") thru ion channels and is abbreviated "S". Is equal to the ratio of current (measured in amps) divided by voltage (measured in volts; note: this comes from ohm's law). It also equals 1/R. One picosiemen equals 10^-12 siemens and is convenient to use for ion channels. For example, the ion channel gramicidin has a conductance of 30 pS for cations. This is equivalent to 6.28 X 10^6 ions per second per applied volt of conductance of cations thru the pore when the concentration of cations is equal on both sides of the membrane.

Single-channel Conductance: a measure of the current that flows thru an open channel in response to a given electrochemical driving force.

Solvation: occurs at the mouth of the pore. During ion permeation, where ion is partially or fully dehydrated and therefore stabilized by interactions with the pore wall.

Streaming Potential: a measurement of ion channel permeability to water molecules. Osmotic gradients are set up and membrane potential simultaneously measured while changing potential. Used to predict water to ion ratios. When water is forced to flow thru a pore by setting up osmotic or hydrostatic pressure differences, they may drag the ions as well. This creates an electric potential difference called the streaming potential.

Subconductance: when conductance is less than what is usually seen. Probably due to subtleties in kinetics of gating and are yet not fully understood. For example, GABA(A) and glycine receptor ion channels appear to have multiple subconductance levels and it is therefore believed that direct transitions between the states can be reached from the closed state. It is believed by some that all channels have subconductance levels, but most are not as obvious as in GABA(A) and glycine receptors.

Tail current: current that flows during the repolarizing phase of an action potential or voltage command. K+ tail currents can be used to determine the reversal potential of voltage-gated K+ currents. In a physiological context, tail currents are often carried by Ca2+ ions and result from the increased driving force as the action potential repolarizes.

Translocation: describes the process of ion transit thru the channel. It is highly dependent upon the driving force for anion permeation and reflects the strength of interaction between the anion and each binding site. More tightly binding ions have a reduced rate of current flow (conductance) due to longer dwell times at any of several possible binding sites within the pore.

Valence: a term to describe the charge of a particle. Na+ and Ca++ have positive valence, while Cl- has negative valence. Moreover, Na+ is monovalent, and Ca++ is divalent. In the Nernst equation and the GHK voltage equation, valence is represented by the variable z.

Voltage: the force created on a charge caused by the separation of charge. Voltage (F) is measured in volts (V). Voltage is equivalent to potential difference.

Voltage-Clamping: a procedure used during study of ion channels, which has the effect of keeping the voltage, produced on a membrane (due ion movement) unchanged. Allows the experimenter to measure only current produced by the ion movement thru the channel. Requires use of a second electrode to measure cell potential. Allows a direct measurement of ionic current across a membrane. This in turn allowed ion channel "kinetic" studies to begin.




i did use two websites a lot so here are the links to the original sites: CFTR Review Page and the Brown University Wiki.