Voltage-dependent Kinetics Research Articles

A fully coupled transient excited state model for the sodium channel. I. Conductance in the voltage clamped case.

The behavior under voltage clamp conditions of a coupled kinetic scheme for the sodium channel is examined. The scheme is given diagrammatically by: Numerical simulations are presented which show that this model fits the voltage clamp data which are well described by the Hodgkin-Huxley equations, but also gives the sorts of behavior anomalous to the Hodgkin-Huxley model which have been seen experimentally. Further, straightforward changes in parameter values are shown to be capable of mimicking the ways in which some axonal preparations differ from others. Detailed, but admittedly heuristic, arguments are presented for the propositions that: 1) the model is minimal; i.e. no simpler kinetic model will fit the array of data simulated, and: 2) the transient excited state is necessary; i.e. no model of comparable simplicity with pure voltage dependent kinetics will fit the array of data simulated.

Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization: experiments in sodium-free bathing media.

Voltage clamp hyperpolarization and depolarization result in currents consistent with depletion and accumulation of potassium in the extracellular clefts o cardiac Purkinje fibers exposed to sodium-free solutions. Upon hyperpolarization, an inward current that decreased with time (id) was observed. The time course of tail currents could not be explained by a conductance exhibiting voltage-dependent kinetics. The effect of exposure to cesium, changes in bathing media potassium concentration and osmolarity, and the behavior of membrane potential after hyperpolarizing pulses are all consistent with depletion of potassium upon hyperpolarization. A declining outward current was observed upon depolarization. Increasing the bathing media potassium concentration reduced the magnitude of this current. After voltage clamp depolarizations, membrane potential transiently became more positive. These findings suggest that accumulation of potassium occurs upon depolarization. The results indicate that changes in ionic driving force may be easily and rapidly induced. Consequently, conclusions based on the assumption that driving force remains constant during the course of a voltage step may be in error.

Membrane excitation through voltage-induced aggregation of channel precursors.

Electrically excitable lipid bilayers show the same voltage-dependent kinetics as nerve and other excitable cells. In the bilayers the gating process involves the voltage-dependent insertion of channel-forming molecules into the hydrocarbon region and their subsequent aggregation by lateral diffusion into an open "barrel stave channel." This process can account quantitatively for the classical Hodgkin-Huxley kinetics including inactivation as well as for certain kinetic features that lie outside the Hodgkin-Huxley domain. The multi- and single-channel kinetics suggest that both the insertion and the aggregation reate constants are voltage-dependent, and it is argued that a voltage-induced lateral phase separation between the lipids and the channel-forming molecules increases the local concentration of channel precursors and their aggregation rates. Because the observed aggregation rates are faster than those calculated from an upper limit of the diffusion constants and the known average concentration in the lipid phase, it is likely that the channel-formers preaggregate at the membrane surface. The structural characteristics of the channel-formers and the evidence supporting a similar excitation mechanism in nerve are discussed.

Kinetic properties and inactivation of the gating currents of sodium channels in squid axon

Associated with the opening and closing of the sodium channels of nerve membrane is a small component of capacitative current, the gating current. After termination of a depolarizing step the gating current and sodium current decay with similar time courses. Both currents decay more rapidly at relatively negative membrane voltages than at positive ones. The gating current that flows during a depolarizing step is diminished by a pre-pulse that inactivates the sodium permeability. A pre-pulse has no effect after inactivation has been destroyed by internal perfusion with the proteolytic enzyme pronase. Gating charge (considered as positive charge) moves outward during a positive voltage step, with voltage dependent kinetics. The time constant of the outward gating current is a maximum at about minus 10 mV, and has a smaller value at voltages either more positive or negative than this value.

The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres

1. The reversal potential of the slow outward current in Purkinje fibres varies with [K](o) in accordance with the expected potassium equilibrium potential. It is concluded that virtually all of this current is carried by potassium ions.2. The magnitude of the current is determined by two separable factors. The first factor is directly proportional to a variable obeying first-order voltage-dependent kinetics of the Hodgkin-Huxley type but with extremely long time constants. The time constants of this variable are extremely sensitive to temperature and the Q(10) over the range 26-38 degrees C is 6.3. The second factor shows inward-going rectification with a marked negative slope in the current-voltage relation beyond about 25 mV positive to the K equilibrium potential. The current-voltage relations measured at different values of [K](o) cross each other on the outward current side of the equilibrium potential.4. The changes in slow potassium current during pace-maker activity have been calculated. It is shown that the mechanism of the pace-maker potential differs in several important respects from that described by Noble's (1962) model. The negative slope in the current-voltage relation appears to be an important factor in generating the last phase of pace-maker depolarization.5. The role of the slow potassium current during the action potential and the consequences of the high temperature dependence of the kinetics are discussed.