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. 2001 Sep;81(3):1245–1254. doi: 10.1016/S0006-3495(01)75782-7

Noncontact dipole effects on channel permeation. IV. Kinetic model of 5F-Trp(13) gramicidin A currents.

N Thompson 1, G Thompson 1, C D Cole 1, M Cotten 1, T A Cross 1, D D Busath 1
PMCID: PMC1301606  PMID: 11509341

Abstract

Nonlinear least squares fitting was used to assign rate constants for the three-barrier, two-site, double-occupancy, single-filing kinetic model for previously reported current-voltage relations of (5F-Indole)Trp(13) gramicidin A and gramicidin A channels (, 75:2830-2844). By judicious coupling of parameters, it was possible to reduce the parameter space from 64 parameters to 24, and a reasonable fit consistent with other experimental data was obtained. The main features of the fit were that fluorination increased the rate constant for translocation by a factor of 2.33, consistent with a free energy change in the translocation barrier of -0.50 kcal/mol, and increased first-ion binding affinity by a factor of 1.13, primarily by decreasing the first-ion exit rate constant. The translocation rate constant was 5.62 times slower in diphytanoyl phosphatidylcholine (DPhPC) bilayers than in monoolein (GMO) bilayers (coupled for the four combinations of peptide and salt), suggesting a 44.2-mV difference in the projection of the interfacial dipole into the channel. Thus fluorination caused increased currents in DPhPC bilayers, where a high interfacial dipole potential makes translocation more rate limiting because the translocation barrier was reduced, and decreased currents in GMO bilayers, where ion exit or entry is rate limiting because these barriers were increased.

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Selected References

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