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Biomedical subjects

C F Stevens

Publications and source records attributed to C F Stevens.

At least 145 records · Page 8Linked to original sources
PubMed1976

A mechanism for spike frequency adaptation.

1. Spike frequency adaptation was studied in large neurones of the marine molluscs Archidoris montereyensis and Anisodoris nobilis. These cells respond to a current step with a rapid rise in spike frequency followed by a gradual decline to a new steady level.2. An exponentially declining current, I(s), was measured when the cell was voltage clamped following an adapting spike train. The initial amplitude of this current depended on the preceding number of spikes and on the voltage to which the cell was clamped. A reversal potential (V(s)) for this current was obtained by clamping to various potentials following a spike train. The time constant (tau(s)) of decay of the current was dependent upon the clamping potential.3. Clamping the membrane potential to a constant test level from various initial levels initiates an exponentially decaying current of similar time constant. The voltage dependence of the steady-state conductance (g(s)a(s)(V, infinity)) associated with this current was determined using this technique.4. Equations for neural repetitive firing (Connor & Stevens, 1971c) were modified by the addition of a term describing these slow membrane currents: [Formula: see text]. The solution to the modified equation was in good agreement with the spike frequency adaptation observed in these cells.

Journal Article↗
PubMed1975

Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox.

1. End-plate currents produced by nerve-released acetylcholine and iontophoretically applied acetylcholine and carbachol have been recorded from voltage-clamped frog cutaneous pectoris neuromuscular junctions made visible with Nomarski differential interference contrast optics. 2. The effectiveness of agonists - that is, the end-plate conductance change produced by a given dose-has been determined as a function of post-junctional membrane potential. 3. As the post-junctional membrane potential is made more negative, nerve-released acetylcholine becomes less effective whereas iontophoretically-applied agonists become more effective. 4. This voltage dependence of agonist effectiveness is mediated neither by end-plate current iontophoresis of agonist into the cleft nor through electric field effects on the esterase. 5. Influences of membrane potential on the opening and closing of end-plate channel gates can account quantitatively for the voltage-dependent effectiveness of both nerve-released and iontophoretically applied agonist.

Acetylcholine↗
PubMed1975

Principles and applications of fluctuation analysis: a nonmathematical introduction.

The mechanisms underlying many of the processes studied by membrane biophysicists are inherently probabilistic, and therefore exhibit random fluctuations around the mean of behavior. These fluctuations reflect the underlying probabilistic mechanism and therefore can sometimes provide information, not otherwise available, about these mechanisms. Fluctuations may be characterized by their spectra which are obtained from a Fourier analysis of the experimental records. When a theory for membrane processes is available, it makes predictions about fluctuation spectra and therefore may be tested by examining these spectra. Theories about gating behavior at the frog neuromuscular junction have been tested in this way, and it has been possible, in addition, to estimate the conductance of one open channel, a quantity not susceptible to direct measurements. Various physical pictures are capable of yielding the same macroscopic behavior for axon membranes, that is, the Hodgkin-Huxley equations, but these various mechanisms predict that the current fluctuations around their mean values should have different characteristics. Fluctuation analysis may, then be of value in elucidating the physical basis for axon conductance changes.

Analysis of Variance↗
PubMed1973

Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction.

1. Acetylcholine produced end-plate current (e.p.c.) noise is shown to be the results of statistical fluctuations in the ionic conductance of voltage clamped end-plates of Rana pipiens.2. These e.p.c. fluctuations are characterized by their e.p.c. spectra which conform to a relation predicted from a simple model of end-plate channel gating behaviour.3. The rate constant of channel closing alpha is determined from e.p.c. spectra and is found to depend on membrane potential V according to the relation alpha = Be(AV) (B = 0.17 msec(-1)+/-0.04 S.E., A = 0.0058 mV(-1)+/-0.0009 S.E. at 8 degrees C) and to vary with temperature T with a Q(10) = 2.77, at -70 mV. A and B in this expression both vary with T and therefore produce a membrane potential dependent Q(10) for alpha.4. Nerve-evoked e.p.c.s and spontaneous miniature e.p.c.s decay exponentially in time with a rate constant which depends exponentially on V. The magnitude and voltage dependence of this decay constant is exactly that found from e.p.c. spectra for the channel closing rate alpha.5. The conductance gamma of a single open end-plate channel has been estimated from e.p.c. spectra and is found not to be detectibly dependent on membrane potential, temperature and mean end-plate current. gamma = 0.32+/-0.0045 (S.E.) x 10(-10) mhos. Some variation in values for gamma occurs from muscle to muscle.6. It is concluded that the relaxation kinetics of open ACh sensitive ionic channels is the rate limiting step in the decay of synaptic current and that this channel closing has a single time constant. The relaxation rate is independent of how it is estimated (ACh produced e.p.c. fluctuations, e.p.c., m.e.p.c.), and is consistent with the hypothesis that individual ionic channels open rapidly to a specific conductance which remains constant for an exponentially distributed duration.7. The voltage and temperature dependence of the channel closing rate constant agree with the predictions of a simple dipole-conformation change model.

Acetylcholine↗
PubMed1972

Inferences about membrane properties from electrical noise measurements.

Four sources of electrical noise in biological membranes, each with a different physical basis, are discussed; the analysis of each type of noise potentially yields a different sort of information about membrane properties. (a) From the thermal noise spectrum, the passive membrane impedance may be obtained, so that thermal noise measurements are essentially equivalent to the type of since wave analysis carried out by Cole and Curtis. (b) If adequately high frequency measurements could be made, the shot noise spectrum should give information about the average motion of a single ion within the membrane. (c) The number of charge carriers and single ion mobilities within the membrane can possibly be inferred from measurements of noise with a 1/f spectrum. Available data indicate, for example, that increases in axon membrane conductance are not achieved by modulations in the mobility of ions within the membrane. (d) Fluctuations arising from the mechanisms normally responsible for membrane conductance changes can produce a type of electrical noise. Analysis of such conductance fluctuations provides a way to assess the validity of various microscopic models for the behavior of individual channels. Two different probabilistic interpretations of the Hodgkin-Huxley equations are investigated here and shown to yield different predictions about the spectrum of conductance fluctuations; thus, appropriate noise measurements may serve to eliminate certain classes of microscopic models for membrane conductance changes. Further, it is shown how the analysis of conductance fluctuations can, in some circumstances, provide an estimate of the conductance of a single channel.

Analysis of Variance↗
PubMed1972

The effect of voltage on the time course of end-plate currents.

1. End-plate currents have been studied in glycerol-treated frog sartorius nerve-muscle preparations with the voltage clamp technique.2. End-plate currents follow a simple exponential time course over most of their declining phase.3. The rate constant alpha that characterizes this exponential decay depends upon membrane potential V according to the relationship alpha (V) = Be(AV), with A = 0.00795 +/- 0.00043 (S.E.) mV(-1) and B = 1.67 +/- 0.04 (S.E.) msec(-1).4. Voltage sensitivity decreases (that is, A in the above equation becomes smaller) as the recording and current-passing electrodes are moved away from the end-plate region.5. The voltage sensitivity of alpha is decreased by decreasing the gain of the voltage clamp amplifier.6. Changing the end-plate current amplitude by curare treatment, by increased calcium ion concentration, and by facilitation and depression has essentially no effect on end-plate current time course.7. When membrane potential is changed step-wise during the decaying phase of the end-plate conductance change, currents begin to decline with a rate constant alpha appropriate to the new membrane potential in less than 0.2 msec.8. Treatment with prostigmine methylsulphate in concentrations up to 50 mug/ml. slows end-plate current decay but has little effect on voltage sensitivity. That is, B in the above equation is decreased by prostigmine treatment, but A is relatively unaffected.

Action Potentials↗
PubMed1972

A quantitative description of end-plate currents.

1. End-plate currents have been studied in glycerol-treated frog sartorius nerve-muscle preparations with the voltage clamp technique.2. The effects of temperature on the decay rate of end-plate currents were investigated over a temperature range from 10 to 30.5 degrees C. The Q(10) for the decay constant of end-plate currents depends somewhat on membrane potential; at - 100 mV the decay constant has a Q(10) of 2.7.3. Peak end-plate current depends non-linearly on membrane potential with a decreasing slope conductance associated with hyperpolarization.4. The ;instantaneous' voltage-current relationship for end-plate channels was determined by causing step changes in membrane potential during end-plate current flow. This relationship appears to be linear.5. The interaction of acetylcholine with its receptor is viewed as being analogous to the first step in enzymic catalysis. On this view, acetylcholine binds to its receptor and induces a conformational change which is responsible for opening end-plate channels. By analogy to the first steps in the catalytic sequence of enzymes, the binding step is very rapid, almost diffusion-limited, and the conformational change is rate-limiting.6. Equations describing this process have been derived. Expressions for the rate constants have also been derived by considering changing dipole moments of the transmitter-receptor complex associated with the conformational change. As the transmitter-receptor complex is in the membrane field, different conformational states have different energies, and the rate of conformational change thus depends on membrane potential. The equations thus derived are shown to account adequately for the time course of end-plate conductance change.

Acetylcholine↗
PubMed1972

Quantal independence and uniformity of presynaptic release kinetics at the frog neuromuscular junction.

1. Amplitude and latency fluctuations of the end-plate potential at the frog neuromuscular junction were studied simultaneously at low temperatures, using intracellular or focal extracellular recording techniques and average quantal contents between 0.5 and 3.2. At the release rates studied, the evoked release of one quantum has in most cases no significant effect on the probability of subsequent quantal release to the same stimulus, confirming the mutual independence of quantal releases in this preparation.3. An equation derived from Poisson's law was applied to a histogram of the latencies of the first quantum released on each of a series of trials, to predict the average quantal content of end-plate responses originating at various times after nerve stimulation. The shape of the predicted time distribution of quantal contents usually agreed closely with that of the experimentally observed time distribution of end-plate response amplitudes. This agreement demonstrates that both the amplitude and the latency fluctuations of the end-plate response result from one presynaptic stochastic process that is uniform in magnitude and time course after each stimulus.4. Analysis of extracellular records from synaptic regions with a history of extensive activity often suggested the existence of depressive interaction among quantal releases, perhaps caused by depletion of the supply of releasable quanta.

Animals↗
PubMed1972

The kinetics of transmitter release at the frog neuromuscular junction.

1. Fluctuations in the latency of focally recorded end-plate currents were analysed to determine the time course of the probabilistic presynaptic process underlying quantal release evoked after single nerve stimuli at the frog neuromuscular junction.2. The early falling phase of the presynaptic probability function can be fitted by a single exponential over two orders of magnitude of quantal release rate. The time constant of the early falling phase is about 0.5 msec at 11 degrees C, and increases with decreasing temperature with a Q(10) of at least 4 over the range 1-12 degrees C.3. After this early exponential fall, quantal release probability returns to control levels with a much slower time course.4. Conditioning nerve stimuli increase the magnitude and slightly prolong the early time course of release evoked by a test stimulus. When facilitation is calculated for matched time intervals following the conditioning and testing stimuli, it is found that the magnitude of the small, late residual tail of release is facilitated by a greater percentage than the magnitude of larger, early portions of release.5. These results are discussed in terms of the hypothesis (Katz & Miledi, 1968) that evoked release and facilitation are mediated by a common presynaptic factor which activates release in a non-linear manner.

Adaptation, Physiological↗
PubMed1971

Inward and delayed outward membrane currents in isolated neural somata under voltage clamp.

1. Membrane current-voltage relationships were investigated under voltage clamp conditions in isolated neural somata of marine gastropods.2. Step depolarizations from the resting potential produce an initial inward current followed by a delayed outward current.3. Inward current appears to be carried by both sodium and calcium ions and displays time and voltage dependent properties similar to those of other excitable membranes.4. Activation and deactivation of the delayed outward current follow a more complicated time course than that of a single exponential raised to a power but can be fitted by the product of two exponential functions.5. Delayed outward current inactivation proceeds with a time constant which decreases as membrane voltage is made more positive. The steady-state levels of inactivation as a function of membrane voltage are related by an S-shaped curve similar to that for K inactivation in squid giant axon.

Animals↗
PubMed1971

Voltage clamp studies of a transient outward membrane current in gastropod neural somata.

1. Outward directed membrane currents have been studied in voltage clamp experiments on isolated neural somata of the marine gastropod Anisodoris.2. Stepping the membrane potential from a hyperpolarized level to a value in the neighbourhood of resting potential (-35 to -50 mV at 5 degrees C) results in an outward current transient, I(A), which is apparently carried by potassium ions.3. The peak amplitude of I(A) is dependent upon both the holding voltage level and the test step voltage while the time courses of development and decay are independent of, or only slightly dependent on, these parameters.4. The developing and decaying phases of I(A) are approximated by exponentials, leading to time constants for development of 10-25 msec and for decay of 220-600 msec over the aggregate of cells studied (data at 5 degrees C). Q(10) for the processes is approximately 3.5. It is concluded that the transport mechanism for I(A) is at least operationally distinct from the mechanism underlying delayed outward current, I(K).

Animals↗
PubMed1971

Prediction of repetitive firing behaviour from voltage clamp data on an isolated neurone soma.

1. Membrane parameters of an isolated neural cell body have been determined by voltage clamp analysis. Data are expressed as membrane ion-specific conductances, leak conductance, and capacitance.2. Three ionic currents are present: Inward, I(I); and two operationally distinct outward currents, I(K) and I(A). Both outward currents are apparently carried by potassium ions.3. Hodgkin-Huxley-like equations were solved for the discharge of two sequential action potentials in response to a constant stimulus current. The digital computer solutions are compared with action potential data recorded from the investigated cell.4. The computed and experimentally measured relationships between firing frequency and stimulus current intensity are compared and are linear over the same portion of the total frequency range.5. Cell behaviour in the latter part of the interspike interval is dominated by the conductance g(A) while g(Na) and g(K) largely determine the character of the action potential and the initial portion of the interspike interval.6. Prehyperpolarization of the membrane activates g(A) and the membrane response to depolarizing current differs markedly from the response elicited when no prehyperpolarization is imposed.

Action Potentials↗