Multi-site, multi-barrier, multi-occupancy models for the electrical behavior of single filing channels like those of gramicidin

Hägglund, Jarl V.; Enos, B.; Eisenman, George

doi:10.1016/0361-9230(79)90077-7

Cited by 22 publications

(8 citation statements)

References 8 publications

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“…pendent upon permeant ion activity -sublinear at low ion activities, and superlinear at high ion activities. The actual behavior of gramicidin A channels is qualitatively consistent with the predictions of the latter type of model (Hladky & Haydon, 1972;H~igglund, Enos & Eisenman, 1979;Andersen & Procopio, 1980). (This model cannot account quantitatively for the shapes of the I-V characteristics at different ion activities.…”

Section: Multiple-ion Occupancysupporting

confidence: 74%

“…These channels thus behave as if the major barrier for ion movement is indeed the translocation step through the channel interior. More detailed investigations of such analogues might help determine the number of cation-binding sites that can be simultaneously occupied in the gramicidin A channel--a question still subject to controversy (H~igglund et al, 1979;Andersen & Procopio, 1980). , 1965;Essig, Kedem & Hill, 1966;Hille & Schwarz, 1978;:…”

Section: Single-channel Conductance As a Function Of Permeant Ion Actmentioning

confidence: 99%

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The gramicidin a channel: A review of its permeability characteristics with special reference to the single-file aspect of transport

1981

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Gramicidin A forms univalent cation-selective channels of approximately 4 A diameter in phospholipid bilayer membranes. The transport of ions and water throughout most of the channel length is by a single-file process; that is, cations and water molecules cannot pass each other within the channel. The implications of this single-file mode of transport for ion movement are considered. In particular, we show that there is no significant electrostatic barrier to ion movement between the energy wells at the two ends of the channel. The rate of ion translocation (e.g., Na+ or Cs+) through the channel between these wells is limited by the necessity for an ion to move six water molecules in single file along with it; this also limits the maximum possible value for channel conductance. At all attainable concentrations of NaCl, the gramicidin A channel never contains more than one sodium ion, whereas even at 0.1 M CsCl, some channels contain two cesium ions. There is no necessity to postulate more than two ion-binding sites in the channel or occupancy of the channel by more than two ions at any time.

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Section: Multiple-ion Occupancysupporting

confidence: 74%

Section: Single-channel Conductance As a Function Of Permeant Ion Actmentioning

confidence: 99%

The gramicidin a channel: A review of its permeability characteristics with special reference to the single-file aspect of transport

1981

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“…It is widely accepted that the channel is filled with water molecules (Levitt et al, 1978;Rosenberg and Finkelstein, 1978 a, b) and is highly cation selective (Myers and Haydon, 1972). Aside from gating, gramicidin shows much of the complex behavior of the K+ channel (Hille, 1975;Armstrong, 1975;Hille and Schwarz, 1978;Hagglund et al, 1979;Andersen 'Rosenberg and Finkelstein (1978b) have made similar measurements in 10 mM NaCl + 100 mM choline chloride and obtained a water permeability about six times smaller than reported here. When they made the measurement, the single channel conductance in 10 mM NaCI was not available.…”

Section: Introductionsupporting

confidence: 71%

Binding constants of Li+, K+, and Tl+ in the gramicidin channel determined from water permeability measurements

Dani¹,

Levitt²

1981

Biophysical Journal

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In an open circuit there can be no net cation flux through membranes containing only cation-selective channels, because electroneutrality must be maintained. If the channels are so narrow that water and cations cannot pass by each other, then the net water flux through those "single-file" channels that contain a cation is zero. It is therefore possible to determine the cation binding constants from the decrease in the average water permeability per channel as the cation concentration in the solution is increased. Three different methods were used to determine the osmotic water permeability of gramicidin channels in lipid bilayer membranes. The osmotic water permeability coefficient per gramicidin channel in the absence of cations was found to be 6 x 10(-14) cm3/s. As the cation concentration was raised, the water permeability decreased and a binding constant was determined from a quantitative fit to the data. When the data were fitted assuming a maximum of one ion per channel, the dissociation constant was 115 mM for Li+, 69 mM for K+, and 2 mM for Tl+.

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“…While the crystal structure data do not demonstrate simultaneous occupancy (i.e., multiple occupancy) within a single 26-A length of channel, the sodium-23 nuclear magnetic resonance data do indicate a second binding site, i.e., a second ion occupancy, becoming significant at concentrations of 100mM and above. Accordingly, mul-tiple occupancy models are required fi'om these studies which, in fact, confirm previous deductions from electrical measurements on gramicidin-doped lipid bilayers (Eisenman, Sandblom & Neher, 1977;Sandblom et al, 1977;Eisenman, Sandblom & Neher, 1978;Urban, Hladky & Haydon, 1978;H~igglund, Enos & Eisenman, 1979;Hladky et al, 1979). Five single filing, multiple occupancy models are considered here in terms of steady-state schemes, steadystate equations, schematic energy profiles and singlechannel currents.…”

Section: Appendix a Multiple Occupancy Models: Steady-state Equationssupporting

confidence: 62%

The malonyl gramicidin channel: NMR-derived rate constants and comparison of calculated and experimental single-channel currents

et al. 1980

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Malonyl gramicidin is incorporated into lysolecithin micelles in a manner which satisfies a number of previously demonstrated criteria for the formation of the transmembrane channel structure. By means of sodium-23 nuclear magnetic resonance, two binding sites are observed: a tight site and a weak site with binding constants of approximately 100 M-1 and 1 M-1 respectively. In addition, off-rate constants from the two sites were estimated from NMR analyses to be kofft congruent to 3 X 10(5)/sec and koffw congruent to 2 X 10(7)/sec giving, with the binding constants, the on-rate constants, kont congruent to 3 X 10(7)/Msec and konw congruent to 2 X 10(7)/Msec. Five different multiple occupancy models with NMR-restricted energy profiles were considered for the purpose of calculating single-channel currents as a function of voltage and concentration utilizing the four NMR-derived rate constants (and an NMR-limit placed on a fifth rate constant for intrachannel ion translocation) in combination with Eyring rate theory for the introduction of voltage dependence. Using the X-ray diffraction results of Koeppe et al. (1979) for limiting the positions of the tight sites, the two-site model and a three-site model in which the weak sites occur after the tight site is filled were found to satisfactorily calculate the experimental currents (also reported here) and to fit the experimental currents extraordinarily well when the experimentally derived values were allowed to vary to a least squares best fit. Surprisingly the "best fit" values differed by only about a factor of two from the NMR-derived values, a variation that is well within the estimated experimental error of the rate constants. These results demonstrate the utility of ion nuclear magnetic resonance to determine rate constants relevant to transport through the gramicidin channel and of the Eyring rate theory to introduce voltage dependence.

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Multi-site, multi-barrier, multi-occupancy models for the electrical behavior of single filing channels like those of gramicidin

Cited by 22 publications

References 8 publications

The gramicidin a channel: A review of its permeability characteristics with special reference to the single-file aspect of transport

The gramicidin a channel: A review of its permeability characteristics with special reference to the single-file aspect of transport

Binding constants of Li+, K+, and Tl+ in the gramicidin channel determined from water permeability measurements

The malonyl gramicidin channel: NMR-derived rate constants and comparison of calculated and experimental single-channel currents

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