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C M Armstrong

Publications and source records attributed to C M Armstrong.

83 records · Page 5Linked to original sources
PubMed1972

The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier.

Quaternary ammonium ions were applied to the inside of single myelinated nerve fibers by diffusion from a cut end. The resulting block of potassium channels in the node of Ranvier was studied under voltage-clamp conditions. The results agree in almost all respects with similar studies by Armstrong of squid giant axons. With tetraethylammonium ion (TEA), pentyltriethylammonium ion (C(5)), or nonyltriethylammonium ion (C(9)) inside the node, potassium current during a depolarization begins to rise at the normal rate, reaches a peak, and then falls again. This unusual inactivation is more complete with C(9) than with TEA. Larger depolarizations give more block. Thus the block of potassium channels grows with time and voltage during a depolarization. The block reverses with repolarization, but for C(9) full reversal takes seconds at -75 mv. The reversal is faster in 120 mM KCl Ringer's and slower during a hyperpolarization to -125 mv. All of these effects contrast with the time and voltage-independent block of potassium, channels seen with external quaternary ammonium ions on the node of Ranvier. External TEA, C(5), and C(9) block without inactivation. The external quaternary ammonium ion receptor appears to be distinct from the inner one. Apparently the inner quaternary ammonium ion receptor can be reached only when the activation gate for potassium channels is open. We suggest that the inner receptor lies within the channel and that the channel is a pore with its activation gate near the axoplasmic end.

Animals↗
PubMed1972

Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons.

Internal Cs(+), Na(+), Li(+), and, to a lesser degree, Rb(+) interfere with outward current through the K pores in voltage clamped squid axons. Addition of 100 mM NaF to the perfusion medium cuts outward current for large depolarizations about in half, and causes negative conductance over a range of membrane voltages. For example, suddenly reducing membrane potential from +100 to +60 mv increases the magnitude of the outward current. Internal Cs(+) and, to a small extent, Li(+), also cause negative conductance. Na(+) ions permeate at least 17 times less well through the K pores than K(+), and Cs(+) does not permeate measurably. The results strongly suggest that K pores have a wide and not very selective inner mouth, which accepts K(+), Na(+), Li(+), Cs(+), tetraethylammonium ion (TEA(+)), and other ions. The diameter of the mouth must be at least 8 A, which is the diameter of a TEA(+) ion. K(+) ions in the mouths probably have full hydration shells. The remainder of the pore is postulated to be 2.6-3.0 A in diameter, large enough for K(+) and Rb(+) but too small for Cs(+) and TEA(+). We postulate that Na(+) ions do not enter the narrower part of the pore because they are too small to fit well in the coordination cages provided by the pore as replacements for the water molecules surrounding an ion.

Animals↗
PubMed1971

Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.

A number of compounds related to TEA(+) (tetraethylammoniumion) were injected into squid axons and their effects on g(K) (the potassium conductance) were determined. In most of these ions a quaternary nitrogen is surrounded by three ethyl groups and a fourth group that is very hydrophobic. Several of the ions cause inactivation of g(K), a type of ionic gating that is not normally seen in squid axon; i.e., after depolarization g(K) increases and then spontaneously decreases to a small fraction of its peak value even though the depolarization is maintained. Observations on the mechanism of this gating show that (a) QA (quaternary ammonium) ions only enter K(+) channels that have open activation gates (the normal permeability gates). (b) The activation gates of QA-occluded channels do not close readily. (c) Hyperpolarization helps to clear QA ions from the channels. (d) Raising the external K(+) concentration also helps to clear QA ions from the channels. Observations (c) and (d) strongly suggest that K(+) ions traverse the membrane by way of pores, and they cannot be explained by the usual type of carrier model. The data suggest that a K(+) pore has two distinct parts: a wide inner mouth that can accept a hydrated K(+) ion or a TEA(+)-like ion, and a narrower portion that can accept a dehydrated or partially dehydrated K(+) ion, but not TEA(+).

Animals↗
PubMed1969

Inactivation of the potassium conductance and related phenomena caused by quaternary ammonium ion injection in squid axons.

Several analogues of the tetraethylammonium (TEA(+)) ion were injected into the giant axon of the squid, and the resultant changes in time course and magnitude of the potassium current (I(K)) were studied. For all the analogues used, three of the ethyl side chains of TEA(+) were left unchanged, while the fourth chain was either lengthened or shortened. Increasing the length of this chain increased binding to the blocking site in the channel by a factor of roughly two for each added CH(2) group. The effect on the rate of entry into the blocking site was relatively slight. Thus the concentration for half-suppression of g(K) decreased by about the same factor of two for each added CH(2). All the analogues caused anomalous or ingoing rectification. The longest chain analogue used, pentyltriethylammonium ion, caused rapid inactivation of g(K), and this inactivation had properties quite similar to g(Na) inactivation. The anomalous rectification and the g(K) inactivation caused by these compounds have the same basic mechanism.

Animals↗
PubMed1966

Time course of TEA(+)-induced anomalous rectification in squid giant axons.

Changes in the voltage clamp currents of squid giant axons wrought by low axoplasmic TEA+ (tetraethylammonium chloride) concentrations (0.3 mM and above) are described. They are: (a) For positive steps from the resting potential in sea water, the K+ current increases, decreases, then increases, instead of increasing monotonically. (b) For positive steps from the resting potential in 440 mM external K+, the current has an exponentially decaying component, whose decay rate increases with axoplasmic [TEA+]. The control currents increase monotonically. (c) For negative steps from the resting potential in 440 mM external K+, the current record has a peak followed by a decay that is slow relative to the control. The control record decreases monotonically. Qualitatively these findings can be described by a simple kinetic model, from which, with one assumption, it is possible to calculate the rate at which K+ ions move through the K+ channels. An interesting conclusion from (c) is that the channels cannot be closed by the normal voltage-sensitive mechanism (described by Hodgkin and Huxley) until they are free of TEA+.

Action Potentials↗
PubMedDate not supplied

Threshold channels--a novel type of sodium channel in squid giant axon.

Sodium channels in nerve and muscle cells are functionally similar across wide phylogenetic boundaries and are usually thought to represent a single, homogeneous population that initiates the action potential at threshold and unerringly transmits it along the surface membrane. In marked contrast, many cell types are known to have several distinct potassium permeability systems. Distinguishable populations of Na channels have been reported in a few cell types, however, including denervated skeletal muscle, embryonic cardiac muscle, Purkinje cell somata and non-myelinated axons at low temperature. We report here that in squid giant axon, in standard experimental conditions, there are two functionally distinct populations of Na channels. The newly discovered population accounts for only a few per cent of the total Na permeability. The channels are selectively activated by small depolarizations and have very slow closing kinetics. Because these channels activate at voltages near the resting potential and tend to stay open for long times, they must dominate behaviour of the axon membrane in the threshold region for action potential initiation.

Animals↗