CCL

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001-es BibID:BIBFORM004933
Első szerző:Panyi György (biofizikus)
Cím:C-type inactivation of a voltage-gated K+ channel occurs by a cooperative mechanism / Panyi, G., Sheng, Z., Tu, L., Deutsch, C.
Dátum:1995
Megjegyzések:The lymphocyte voltage-gated K+ channel, Kv1.3, inactivates by a C-type process. We have elucidated the molecular basis for this process using a kinetic analysis of wild-type and mutant (A413V) Kv1.3 homo- and heteromultimeric currents in a mammalian lymphoid expression system. The medians of the measured inactivation time constants for wild-type and A413V homotetrameric currents are 204 and 4 ms, respectively. Co-expression of these subunits produces heteromultimeric channels manifesting inactivation kinetics intermediate between those of wild-type and A413V homomultimers. We have considered several models in which each subunit acts either independently or cooperatively to produce the observed inactivation kinetics. The cooperative model gives excellent fits to the data for any heteromultimeric composition of subunits, clearly distinguishing it from the independent models. In the cooperative model, the difference in free energy between the open and inactivated states of the channel is invariant with subunit composition and equals approximately 1.5 kcal/mol. Each subunit contributes equally to the activation free energy for transitions between open and inactivated states, with an A413V subunit decreasing the free energy barrier for inactivation (and for recovery from inactivation) by approximately 0.6 kcal/mol. Our results are consistent with a physical model in which the outer mouth of the channel constricts during C-type inactivation.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Animal
biosynthesis
Cells,Cultured
Electrophysiology
Human
Kinetics
Macromolecular Systems
Mathematics
Membrane Potentials
metabolism
methods
Mice
Models,Theoretical
Mutagenesis,Site-Directed
physiology
Plasmids
Point Mutation
Potassium
Potassium Channels
Recombinant Proteins
Transfection
Megjelenés:Biophysical Journal. - 69 : 3 (1995), p. 896-903. -
További szerzők:Sheng, Zufang Tu, LiWei Deutsch, Carol
Internet cím:elektronikus változat
elektronikus változat
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