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Biomedical subjects

C F Stevens

Publications and source records attributed to C F Stevens.

At least 127 records · Page 7Linked to original sources
PubMed1981

The effect of tetramethylammonium on single sodium channel currents.

Voltage-dependent Na conductance of rat myotubes was studied by patch recordings of single-channels. The patches were excised from the cell with the patch electrode, and the cytoplasmic surface was bathed in either CsF or tetramethylammonium (TMA)-F. Inward currents were examined from -20 to -50 mV. In this range Cs and TMA both appeared to be nearly impermeant, but TMA blocked the channel in a voltage-dependent manner. A first-order blocking site was located a maximum of 89% of the way through the membrane field from the cytoplasmic surface.

Animals↗
PubMed1980

Ion conductance and ion selectivity of potassium channels in snail neurones.

Delayed potassium channels were studied in internally perfused neurone somata from land snails. Relaxation and fluctuation analysis of this class of ion channels revealed Hodgkin-Huxley type K channels with an average single channel conductance (gamma K) of 2.40 +/- 0.15 pS. The conductance of open channels is independent of voltage and virtually all K channels seem to be open at maximum K conductance (gk) of the membrane. Voltage dependent time constants of activation of gK, calculated from K current relaxation and from cut-off frequencies of power spectra, are very similar indicating dominant first-order kinetics. Ion selectivity of K channels was studied by ion substitution in the external medium and exhibited the following sequence: Tl+ greater than K+ greater than Rb+ greater Cs+ greater than NH4+ greater Li+ greater than Na+. The sequence of the alkali cations does not conform to any of the sequences predicted by Eisenman's theory. However, the data are well accommodated by a new theory assuming a single rate-limiting barrier that governs ion movement through the channel.

Animals↗
PubMed1980

Rate-limiting step of inhibitory post-synaptic current decay in Aplysia buccal ganglia.

1. In neurones BL and BR 3, 6, 8, 9, 10 and 11 of Aplysia buccal ganglia, cholinergic inhibitory post-synaptic potentials are produced by activity in either of two presynaptic cells. In order to analyse the synaptic conductance change, neurones were voltage-clamped inhibitory post-synaptic currents (i.p.s.c.) recorded. 2. The synaptic conductance change rises to an average peak value of 0.65 micromho and decays exponentially with single time constant tau of 19 msec. 3. We have attempted to identify the rate-limiting step responsible for i.p.s.c. decay from among the following possibilities: (1) acetylcholine (ACh) supply, (2) ACh removal by diffusion, (3) ACh removal by hydrolysis or (4) a slow unbinding or conformational change closing open synaptic current channels. 4. Cooling prolongs tau, with Q10 of 5.2. Cooling and eserine treatment together produce greatly prolonged, exponentially decaying i.p.s.c.s with tau > 150 msec. These results suggest that ACh removal, either by diffusion or hydrolysis, is not the rate-limiting step. 5. Prolonging synaptic action potential time course with intracellular injection of tetraethylammonium broadens the i.p.s.c. peak but does not affect the decay tail, suggesting that the rate-limiting step is not ACh release. 6. The spectrum of ACh-induced current fluctuations is fitted by a double Lorentzian with cut-off frequencies of 7.8 and 47 Hz. The frequency of the slower component corresponds to the macroscopic i.p.s.c. decay tau. 7. We conclude that a slow conformational change closing open synaptic current channels is likely to determine i.p.s.c. decay. We cannot, however, exclude either delayed diffusion or a late tail of slow ACh release as possibilities.

Acetylcholine↗
PubMed1979

The neuron.

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Acetylcholine↗
PubMed1978

Interactions between intrinsic membrane protein and electric field. An approach to studying nerve excitability.

We have approached the problem of nerve excitability through three questions: (a) What is the diagram for a channel? That is, what conformational states can the protein assume, and what transitions between these conformations are permitted? (b) What is the channel conductance associated with each conformation the channel can assume? (c) How do the rates for conformational transition depend upon membrane potential? These three questions arise from a standard statistical mechanical treatment of a nerve membrane containing several classes of identical, independent channels. Gating of channels, in this view, is associated with conformational changes of the channel protein, and it is assumed these conformations are distinct. The precise formulation of these questions is presented in terms of the theoretical treatment, and the approaches we have taken to answer the questions are indicated. Our present results indicate: Transition rates should depend exponentially on membrane potential over a limited voltage range, but probably will show a more complex dependence for extremes of the range; channels probably can take on only two conductances, open and shut, but more complicated situations are not entirely excluded; the diagram for a channel cannot be determined from standard voltage clamp data alone, but by studying gating currents and conductance fluctuations, it should be possible to select between alternative plausible physical mechanisms.

Biological Transport↗
PubMed1978

An analysis of the dose-response relationship at voltage-clamped frog neuromuscular junctions.

1. Frog neuromuscular junctions were viewed with Nomarski optics and voltage clamped. Agonist was applied ionophoretically and agonist concentrations were measured using a micro-electrode sensitive to quaternary amines. 2. The dose-response relationship was studied using the agonists carbamylcholine, suberyldicholine and hydroxyphenyl-propyltrimethylammonium. 3. With all of these agonists, it appeared that the ACh receptor could be active when either one or two agonist binding sites were occupied. The receptor was much more likely to be active when both sites were occupied. Agonist dissociation constants and receptor activation probabilities were estimated by non-linear regression techniques for several possible receptor activation schemes.

Animals↗
PubMed1978

Synaptic actions of acetylcholine: problems for future research.

Acetylcholine is currently believed to act on postsynaptic membranes by binding to a specific membrane receptor protein and inducing a conformational change that opens a channel for ion fluxes. This conformational change is viewed as rate limiting, with the agonist binding-dissociation step being very fast. The open channel has a conductance of 27 pS, and the gating molecule responsible for the channel opening and closing undergoes a dipole moment change of 50 D in making the open-closed transition. Although this picture accounts quantitatively for many aspects of acetylcholine action, certain of the underlying assumptions are untested, and the view is incomplete or unsatisfactory in several other ways. Four goals for future research, then, are: 1) To determine whether conformational change or agonist dissociation is the rate limiting step; present interpretations assume the conformation change is rate limiting, but available data are equally consistent with the alternative assumption. 2) To discover the nature and significance of direct anticholinesterase actions on the channel gating process; evidence is available that some direct actions occur, but these have not yet been studied. 3) To fit the process of desensitization into the present picture of acetylcholine actions. 4) To merge the pictures of acetylcholine-receptor interactions that are being developed concurrently by physiologists and biochemists. Achieving this goal should eventually lead to an understanding of how intrinsic proteins regulate membrane ionic fluxes.

Acetylcholine↗
PubMed1977

Study of membrane permeability changes by fluctuation analysis.

The molecular basis of the changes in membrane permeability that underlie the nerve impulse can be studied by statistical analysis of the random fluctuations in current through the nerve membrane. Such "noise analysis" has already begun to clarify the nature of the gating mechanisms that control the flow of ions across the membrane at the neuromuscular junction.

Acetylcholine↗
PubMed1976

A comment on Martin's relation.

In the limit of slowly varying synaptic conductance changes, a quantity proportional to the quantal content of a synaptic potential is provided by Martin's formula: 1/(VO/Vp-1), where Vp is the peak amplitude of the synaptic potential and Vo is the synaptic equilibrium potential. If the synaptic conductance change is not slowly varying on the time scale of the postsynaptic cell's membrane time constant, Martin's formula overestimates the effects of nonlinear summation and provides an upper limit for the actual quantal content. In the limit of rapidly varying synaptic conductance changes the quantity ln(1/[1-Vp/Vo]) is proportional to the quantal content. This formula underestimates the effects of nonlinear summation and gives a lower limit for the quantal content for cases in which the synaptic conductance is not rapidly varying. These two formulas used together provide upper and lower bounds to the correction for nonlinear summation of postsynaptic potentials.

Electric Conductivity↗