Micro- and macrokinetic behavior of the subunit gating channel

Abstract

Summary.The concept of a channel that builds up from subunit molecules by way of aggregation can provide the framework for a unified description of electrical excitability in cell and model membranes at the micro-and macrokinetic level. Monte Carlo simulations of the microkinetics of a subunit channel predict two extreme kinds of gating behavior. Depending on the reaction parameters, a simulation can result either in single-step open-closed microkinetics, as elucuidated by noise analysis of excitable cell membranes, or in records resembling the multi-step conductance bursts that are measured in lipid bilayers modified by alamethicin. Numerical calculations of the voltage-clamp macrokinetics for the two cases reveal that the set of parameters that produces nerve-and muscle-like fluctuations gives Hodgkin-Huxley-type time courses, while the set that results in alamethicin-like fluctuation behavior gives alamethicin-like macrokinetics. The macrokinetic behavior is generated by summing microkinetic simulations for the nerve and the alamethicin case.

Activation of squid axon K+ channels. Ionic and gating current studies.

“…We have tried variations of the box models proposed for Na' channel activation (Armstrong and Bezanilla, 1977;Bezanilla and Taylor, 1982) and they offer no improvement. The aggregation model of Baumann and Easton (1980) is eliminated on theoretical grounds as it cannot produce gating currents with nonartifactual rising phases (Baumann and Easton, 1982). The aggregation model introduced by Muller and Peskin (1981) to describe monazomycin conductance kinetics can produce gating currents with rising phases, but those authors were unable to fit their model to K' channel ionic currents.…”

Relationship between membrane excitability and single channel open-close kinetics

“…Our primary purpose in using the Hodgkin and Huxley (1952) model was to illustrate a novel stimulation technique. Other investigators have presented simulations for voltage jumps or steady-state voltage-clamp conditions (Colquhoun and Hawkes, 1977;Baumann and Easton, 1980;Lecar and Sachs, 1981). These authors did not present results for conditions in which either the rate constants for transitions between states are effectively time dependent or the membrane is unclamped.…”

Novel kinetics in the sodium conductance system predicted by the aggregation model of channel gating

“…3. The detailed assumptions that form the basis of these calculations are given in Baumann and Easton, 1980. Specifically, a temperature of 10°C, a gating charge of 1, a total subunit concentration of 1 M, frequency factors of 10,000 reactions/s (reactions/s-liter in the case of bimolecular reactions), and activation energies of 0 kJ/mol are assumed with the exception of the voltage-dependent step from chemically inert to active monomer where the activation energy is 2 kJ/mol, and the dimer-to-monomer reaction where it is 15 kJ/mol.…”