scholarly journals Selective modification of sodium channel gating in lobster axons by 2, 4, 6-trinitrophenol: Evidence for two inactivation mechanisms.

1975 ◽  
Vol 66 (6) ◽  
pp. 765-779 ◽  
Author(s):  
G S Oxford ◽  
J P Pooler
Keyword(s):  
Time Course ◽  
Sodium Currents ◽  
Voltage Range ◽  
Sodium Conductance ◽  
Gap Technique ◽  
Voltage Curve ◽  
Sucrose Gap ◽  
Sodium Inactivation ◽  
Kinetics Of ◽  
Double Sucrose Gap Technique

Trinitrophernol (TNP) selectively alters the sodium conductance system of lobster giant axons as measured in current clamp and voltage clamp experiments using the double sucrose gap technique. TNP has no measurable effect on potassium currents but reversibly prolongs the time-course of sodium currents during maintained depolarizations over the full voltage range of observable currents. Action potential durations are increased also. Tm of the Hodgkin-Huxley model is not markedly altered during activation of the sodium conductance but is prolonged during removal of activation by repolarization, as observed in sodium tail experiments. The sodium inactivation versus voltage curve is shifted in the hyperpolarizing direction as is the inactivation time constant curve, measured with conditioning voltage steps. This shift speeds the kinetics of inactivation over part of the same voltage range in which sodium currents are prolonged, a contradiction incompatible with the Hodgkin-Huxley model. These results are interpreted as support for a hypothesis of two inactivation processes, one proceeding directly from the resting state and the other coupled to the active state of sodium conductance.

scholarly journals Initial conditions and the kinetics of the sodium conductance in Myxicola giant axons. I. effects on the time-course of the sodium conductance.

1978 ◽  
Vol 72 (6) ◽  
pp. 863-877 ◽  
Author(s):  
R Hahin ◽  
L Goldman
Keyword(s):  
Time Course ◽  
Initial Conditions ◽  
Coupled Model ◽  
Time Shift ◽  
Activation Process ◽  
Time Behavior ◽  
Giant Axons ◽  
Sodium Conductance ◽  
Fast Activation ◽  
Kinetics Of

The effects of conditioning polarizations, ranging from--150 to 0 mV and of durations from 50 mus to 30 ms, on the time-course of GNa during test steps in potential were studied in Myxicola giant axons. Beyond the effects of conditioning polarizations on the amplitude of GNa, the only effect was to produce a translation of GNa(t) along the time axis without a change in shape. For depolarizing conditioning potentials, Hodgkin-Huxley kinetics predict time shifts about threefold greater than found experimentally, whereas the predictions of the coupled model of Goldman (1975. Biophys. J. 15:119--136) were in approximate agreement with our experiments. The time shifts developed over an exponential time-course as the conditioning pulse duration was increased. The time constant of development of the time shift was considerably faster than, and showed the opposite dependency on potential from, the values predicted by both models. It had a mean Q10 of 1/2.50. This fast activation process cannot account for the observed rise time behavior of GNa, suggesting that there is an additional activation process. All results are consistent with the idea that the gating structure displays more than three states, with state intermediate between rest and conducting.

scholarly journals Effects of Internal Divalent Cations on Voltage-Clamped Squid Axons

1974 ◽  
Vol 63 (6) ◽  
pp. 675-689 ◽  
Author(s):  
Ted Begenisich ◽  
Carl Lynch
Keyword(s):  
Time Course ◽  
Voltage Dependence ◽  
Divalent Cations ◽  
Sodium Current ◽  
Ionic Currents ◽  
Zinc Concentrations ◽  
Sodium Inactivation ◽  
Kinetics Of ◽  
Internal Calcium ◽  
Reversible Reduction

We have studied the effects of internally applied divalent cations on the ionic currents of voltage-clamped squid giant axons. Internal concentrations of calcium up to 10 mM have little, if any, effect on the time-course, voltage dependence, or magnitude of the ionic currents. This is inconsistent with the notion that an increase in the internal calcium concentration produced by an inward calcium movement with the action potential triggers sodium inactivation or potassium activation. Low internal zinc concentrations (∼1 mM) selectively and reversibly slow the kinetics of the potassium current and reduce peak sodium current by about 40% with little effect on the voltage dependence of the ionic currents. Higher concentrations (∼10 mM) produce a considerable (ca. 90%) nonspecific reversible reduction of the ionic currents. Large hyperpolarizing conditioning pulses reduce the zinc effect. Internal zinc also reversibly depolarizes the axon by 20–30 mV. The effects of internal cobalt, cadmium, and nickel are qualitatively similar to those of zinc: only calcium among the cations tested is without effect.

scholarly journals Voltage-dependence of Ion Permeation in Cyclic GMP–gated Ion Channels Is Optimized for Cell Function in Rod and Cone Photoreceptors

2002 ◽  
Vol 119 (4) ◽  
pp. 341-354 ◽  
Author(s):  
Tsuyoshi Ohyama ◽  
Arturo Picones ◽  
Juan I. Korenbrot
Keyword(s):  
Ion Channels ◽  
Cyclic Nucleotide ◽  
Time Course ◽  
Cell Function ◽  
Membrane Voltage ◽  
Rate Theory ◽  
Ion Permeation ◽  
Voltage Range ◽  
Kinetics Of ◽  
Gated Ion Channels

The kinetics of the photocurrent in both rod and cone retinal photoreceptors are independent of membrane voltage over the physiological range (−30 to −65 mV). This is surprising since the photocurrent time course is regulated by the influx of Ca2+ through cGMP-gated ion channels (CNG) and the force driving this flux changes with membrane voltage. To understand this paradigm, we measured Pf, the fraction of the cyclic nucleotide–gated current specifically carried by Ca2+ in intact, isolated photoreceptors. To measure Pf we activated CNG channels by suddenly increasing free 8-Br-cGMP in the cytoplasm of rods or cones loaded with a caged ester of the cyclic nucleotide. Simultaneous with the uncaging flash, we measured the cyclic nucleotide–dependent changes in membrane current and fluorescence of the Ca2+ binding dye, Fura-2, also loaded into the cells. We determined Pf under physiological solutions at various holding membrane voltages between −65 and −25 mV. Pf is larger in cones than in rods, but in both photoreceptor types its value is independent of membrane voltage over the range tested. This biophysical feature of the CNG channels offers a functional advantage since it insures that the kinetics of the phototransduction current are controlled by light, and not by membrane voltage. To explain our observation, we developed a rate theory model of ion permeation through CNG channels that assumes the existence of two ion binding sites within the permeation pore. To assign values to the kinetic rates in the model, we measured experimental I-V curves in membrane patches of rods and cones over the voltage range −90 to 90 mV in the presence of simple biionic solutions at different concentrations. We optimized the fit between simulated and experimental data. Model simulations describe well experimental photocurrents measured under physiological solutions in intact cones and are consistent with the voltage-independence of Pf, a feature that is optimized for the function of the channel in photoreceptors.

Kinetics of slow changes in membrane potential induced by direct current polarization of single nerve fibers

1958 ◽  
Vol 196 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Gordon M. Schoepfle
Keyword(s):  
Membrane Potential ◽  
Direct Current ◽  
Time Course ◽  
Nerve Fibers ◽  
Slow Potential ◽  
Slow Drift ◽  
Single Nerve ◽  
Sodium Inactivation ◽  
Kinetics Of ◽  
Limiting Value

A direct current pulse applied to an isolated single fiber of the frog sciatic induces a slow drift in membrane potential which can be described by a single exponential term throughout most of its time course. Both magnitude and time parameter are functions of pre-existent membrane potential. With increasing cathodal polarization the magnitude of the drift approaches a limiting value which is dependent only on the duration of the polarizing pulse. No change in resistance is detectable with brief test transient pulses. In fibers sufficiently hyperpolarized to minimize sodium inactivation it is observed that impulses fired off at any time during the course of the slow potential drift are characterized by identical peak values of membrane potential. This indicates that active firing results in a short circuiting of the mechanism responsible for the slow drift. Whereas the data presented favor a change in some e.m.f. as responsible for the slow drift, there exists strong evidence that the potassium emf remains constant.

Voltage control during inward current flow in rat ventricular muscle using a double sucrose gap technique

1979 ◽  
Vol 57 (1) ◽  
pp. 124-127 ◽  
Author(s):  
O. F. Schanne ◽  
M. D. Payet ◽  
E. Ruiz P.-Ceretti
Keyword(s):  
Membrane Potential ◽  
Time Course ◽  
Voltage Control ◽  
State Level ◽  
Slow Inward Current ◽  
Ventricular Muscle ◽  
Time Intervals ◽  
Inward Current ◽  
Gap Technique ◽  
Sucrose Gap

In rat ventricular muscle, measurements of the membrane potential with microelectrodes during depolarizing voltage steps showed that deviation of the membrane potential from the command signal were never larger than 15 mV during flow of the fast inward current and that voltage control was regained within 15 ms after the beginning of the voltage step. During the flow of the slow inward current, tail currents elicited by interrupting the time course of the slow current at different time intervals returned exponentially to the steady-state level, thus indicating acceptable voltage control. It is concluded that rat ventricular muscle is a rather favorable preparation for voltage-clamp experiments and this is attributed mainly to the geometry of the preparation.

scholarly journals Effect of sea anemone toxins on the sodium inactivation process in crayfish axons.

1983 ◽  
Vol 81 (3) ◽  
pp. 305-323 ◽  
Author(s):  
A Warashina ◽  
S Fujita
Keyword(s):  
Time Course ◽  
Early Stage ◽  
Sea Anemone ◽  
Na Channels ◽  
Current Profile ◽  
Anemonia Sulcata ◽  
Sodium Inactivation ◽  
Na Inactivation ◽  
Inactivation Process ◽  
Kinetics Of

The effect of sea anemone toxins from Parasicyonis actinostoloides and Anemonia sulcata on the Na conductance in crayfish giant axons was studied under voltage-clamp conditions. The toxin slowed the Na inactivation process without changing the kinetics of Na activation or K activation in an early stage of the toxin effect. An analysis of the Na current profile during the toxin treatment suggested an all-or-none modification of individual Na channels. Toxin-modified Na channels were partially inactivated with a slower time course than that of the normal inactivation. This slow inactivation in steady state decreased in its extent as the membrane was depolarized to above -45 mV, so that practically no inactivation occurred at the membrane potentials as high as +50 mV. In addition to inhibition of the normal Na inactivation, prolonged toxin treatment induced an anomalous closing in a certain population of Na channels, indicated by very slow components of the Na tail current. The observed kinetic natures of toxin-modified Na channels were interpreted based on a simple scheme which comprised interconversions between functional states of Na channels. The voltage dependence of Parasicyonis toxin action, in which depolarization caused a suppression in development of the toxin effect, was also investigated.

scholarly journals Studies on Calcium and Sodium in Uterine Smooth Muscle Excitation under Current-Clamp and Voltage-Clamp Conditions

1971 ◽  
Vol 58 (3) ◽  
pp. 322-339 ◽  
Author(s):  
Nels C. Anderson ◽  
Fidel Ramon ◽  
Ann Snyder
Keyword(s):  
Smooth Muscle ◽  
Voltage Clamp ◽  
Current Clamp ◽  
Uterine Smooth Muscle ◽  
Gap Technique ◽  
Steady State Current ◽  
Sucrose Gap ◽  
High Concentrations ◽  
Muscle Calcium ◽  
Double Sucrose Gap Technique

The objective of these studies was to define the roles of calcium and sodium in uterine smooth muscle excitation. The double sucrose-gap technique was used for current-clamp and voltage-clamp experiments. It was shown that neither sodium nor calcium alone is capable of supporting excitation in estrogen-dominated uterine smooth muscle. Calcium dependence was explained in part by increased membrane "leakage" current in calcium-free solution and calcium control of the voltage dependence of the early transient conductance. High concentrations of TTX did not affect the magnitude of the peak transient current while La+++, Mn++, and Co++ greatly reduced or abolished it and decreased the steady-state current. From these and other data it was concluded that the regenerative mechanism in uterine smooth muscle has the functional characteristics of a single transient conductance channel whose activation requires the presence of both sodium and calcium. Insensitivity to TTX indicates that the molecular structure of the channel is unlike that in certain sodium-dependent systems, while the effects of La+++, Mn++, Co++, and Ca++ reveal a similar dependence of conductances on extracellular polyvalent cations.

scholarly journals Temperature Dependence of Accommodation and Excitation in Space-Clamped Axons

1968 ◽  
Vol 51 (6) ◽  
pp. 759-769 ◽  
Author(s):  
Rita Guttman ◽  
Keyword(s):  
Temperature Dependence ◽  
Experimental Results ◽  
Square Wave ◽  
Linear Current ◽  
Gap Technique ◽  
Sucrose Gap ◽  
Double Sucrose Gap Technique

Accommodation and excitation in space-clamped squid axons were studied with the double sucrose gap technique, using linear current ramps, short (50 µsec) square wave pulses, and rheobasic square wave pulses as stimuli. The temperature was varied from 5° to 35°C. Experimental results showed a Q10 for accommodation which was 44% higher than that for excitation. Yet calculations on the basis of the Hodgkin-Huxley equations predict equal Q10's for excitation and accommodation. Although the Hodgkin-Huxley equations are spectacularly successful for so many nerve phenomena, the differences between calculations of accommodation and these experiments, which were designed to test the equations, show that the equations need modification in this area.

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