Gating current "fractionation" in crayfish giant axons

Starkus, John G.; Rayner, Martin D.

doi:10.1016/s0006-3495(91)82146-4

Cited by 16 publications

(22 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the same preparation, additional evidence for a fast component has also come from the result of frequency domain analysis techniques (F. Bezanilla, personal communication). More recent studies (Starkus and Rayner 1991) have shown that the relaxation time constant and charge magnitude of the fast component at one potential (-20 mV) are comparable with our data. In the crayfish giant axon preparation, a component having a similar form to that observed here in the squid has been reported by Starkus et al (1981) in the total ON displacement current.…”

Section: Evidence For a Fast Displacement Charge From Other Studiessupporting

confidence: 92%

The early phase of sodium channel gating current in the squid giant axon

Forster

Greeff

1992

Eur Biophys J

View full text Add to dashboard Cite

A fast component of displacement current which accompanies the sodium channel gating current has been recorded from the membrane of the giant axon of the squid Loligo forbesii. This component is characterized by relaxation time constants typically shorter than 25 microseconds. The charge displaced accounts for about 10% (or 2 nC/cm2) of the total displacement charge attributed to voltage-dependent sodium channels. Using a low noise, wide-band voltage clamp system and specially designed voltage step protocols we could demonstrate that this component: (i) is not a recording artifact; (ii) is kinetically independent from the sodium channel activation and inactivation processes; (iii) can account for a significant fraction of the initial amplitude of recorded displacement current and (iv) has a steady state charge transfer which saturates for membrane potentials above +20 mV and below -100 mV. This component can be modelled as a single step transition using the Eyring-Boltzmann formalism with a quantal charge of 1 e- and an asymmetrical energy barrier. Furthermore, if it were associated with the squid sodium channel, our data would suggest one fast transition per channel. A possible role as a sodium channel activation trigger, which would still be consistent with kinetic independence, is discussed. Despite uncertainties about its origin, the property of kinetic independence allows subtraction of this component from the total displacement current to reveal a rising phase in the early time course of the remaining current. This will have to be taken into account when modelling the voltage-dependent sodium channel.

show abstract

Section: Evidence For a Fast Displacement Charge From Other Studiessupporting

confidence: 92%

The early phase of sodium channel gating current in the squid giant axon

Forster

Greeff

1992

Eur Biophys J

View full text Add to dashboard Cite

show abstract

“…The maximum time required to reach this plateau current, at negative test potentials, defines the minimum prepulse duration required to characterize the h. curve. In crayfish axons (see Starkus and Rayner, 1991) this plateau is less obvious and the "steady-state" 'Na decays, with time constants > 100 ms, to very small levels at all test potentials. Nevertheless, an apparent break between fast and slow falling phase kinetics occurs within about 2 ms in our axons even at near threshold potentials.…”

Section: Time Course Of Equilibration During Depolarizing Prepulsesmentioning

confidence: 98%

Steady-state availability of sodium channels. Interactions between activation and slow inactivation

Ruben¹,

Starkus²,

Rayner³

1992

Biophysical Journal

Self Cite

View full text Add to dashboard Cite

Changes in holding potential (Vh), affect both gating charge (the Q(Vh) curve) and peak ionic current (the F(Vh) curve) seen at positive test potentials. Careful comparison of the Q(Vh) and F(Vh) distributions indicates that these curves are similar, having two slopes (approximately 2.5e for Vh from -115 to -90 mV and approximately 4e for Vh from -90 to -65 mV) and very negative midpoints (approximately -86 mV). Thus, gating charge movement and channel availability appear closely coupled under fully-equilibrated conditions. The time course by which channels approach equilibration was explored using depolarizing prepulses of increasing duration. The high slope component seen in the F(Vh) and Q(Vh) curves is not evident following short depolarizing prepulses in which the prepulse duration approximately corresponds to the settling time for fast inactivation. Increasing the prepulse duration to 10 ms or longer reveals the high slope, and left-shifts the midpoint to more negative voltages, towards the F(Vh) and Q(Vh) distributions. These results indicate that a separate slow-moving voltage sensor affects the channels at prepulse durations greater than 10 ms. Charge movement and channel availability remain closely coupled as equilibrium is approached using depolarizing pulses of increasing durations. Both measures are 50% complete by 50 ms at a prepulse potential of -70 mV, with proportionately faster onset rates when the prepulse potential is more depolarized. By contrast, charge movement and channel availability dissociate during recovery from prolonged depolarizations. Recovery of gating charge is considerably faster than recovery of sodium ionic current after equilibration at depolarized potentials. Recovery of gating charge at -140 mV, is 65% complete within approximately 100 ms, whereas less than 30% of ionic current has recovered by this time. Thus, charge movement and channel availability appear to be uncoupled during recovery, although both rates remain voltage sensitive. These data suggest that channels remain inactivated due to a separate process operating in parallel with the fast gating charge. We demonstrate that this behavior can be simulated by a model in which the fast charge movement associated with channel activation is electrostatically-coupled to a separate slow voltage sensor responsible for the slow inactivation of channel conductance.

show abstract

“…Given that the cyclical model shown in Fig. 8 applies to activation of the DHP-sensitive Ca channels as well as the Na channel (Alicata et al, 1990;Starkus and Rayner, 1991) and K channel (Zagotta et al, 1994;and Starkus et al, 1995), it is reasonable to propose that voltagesensitive gating transitions occur early in the Ca channel activation sequence and that it is these processes which could underlie the role of the voltage sensor and yield the rapid E-C coupling in skeletal muscle, through either electrostatic or allosteric linkage to the ryanodine receptor Ca release channel.…”

Section: Dhp Receptors As Fast E-c Coupling Voltage Sensor and Slow mentioning

confidence: 99%

Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating.

Gonzalez

Chen

1996

The Journal of General Physiology

View full text Add to dashboard Cite

Dihydropyridine (DHP) receptors of the transverse tubule membrane play two roles in excitationcontraction coupling in skeletal muscle: (a) they function as the voltage sensor which undergoes fast transition to control release of calcium from sarcoplasmic reticulum, and (b)they provide the conducting unit of a slowly activating L-type calcium channel. To understand this dual function of the DHP receptor, we studied the effect of depolarizing conditioning pulse on the activation kinetics of the skeletal muscle DHP-sensitive calcium channels reconstituted into lipid bilayer membranes. Activation of the incorporated calcium channel was imposed by depolarizing test pulses from a holding potential of -80 mV. The gating kinetics of the channel was studied with ensemble averages of repeated episodes. Based on a first latency analysis, two distinct classes of channel openings occurred after depolarization: most had delayed latencies, distributed with a mode at 70 ms (slow gating); a small number of openings had short first latencies, <12 ms (fast gating). A depolarizing conditioning pulse to +20 mV placed 200 ms before the test pulse (-10 mV), led to a significant increase in the activation rate of the ensemble averaged-current; the time constant of activation went from "fin = 110 ms (reference) to T,,~ = 45 ms after conditioning. This enhanced activation by the conditioning pulse was due to the increase in frequency of fast open events, which was a steep function of the intermediate voltage and the interval between the conditioning pulse and the test pulse. Additional analysis demonstrated that fast gating is the property of the same individual channels that normally gate slowly and that the channels adopt this property after a sojourn in the open state. The rapid secondary activation seen after depolarizing prepulses is not compatible with a linear activation model for the calcium channel, but is highly consistent with a cyclical model. A six-state cyclical model is proposed for the DHP-sensitive Ca channel, which pictures the normal pathway of activation of the calcium channel as two voltagedependent steps in sequence, plus a voltage-independent step which is rate limiting. The model reproduced well the fast and slow gating modes of the calcium channel, and the effects of conditioning pulses. It is possible that the voltage-sensitive gating transitions of the DHP receptor, which occur early in the calcium channel activation sequence, could underlie the role of the voltage sensor and yield the rapid excitation-contraction coupling in skeletal muscle, through either electrostatic or allosteric linkage to the ryanodine receptors/calcium release channels.

show abstract

Gating current "fractionation" in crayfish giant axons

Cited by 16 publications

References 47 publications

The early phase of sodium channel gating current in the squid giant axon

The early phase of sodium channel gating current in the squid giant axon

Steady-state availability of sodium channels. Interactions between activation and slow inactivation

Fast activation of dihydropyridine-sensitive calcium channels of skeletal muscle. Multiple pathways of channel gating.

Contact Info

Product

Resources

About