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001-es BibID:	BIBFORM004844
Első szerző:	Somodi Sándor (belgyógyász)
Cím:	pH-dependent modulation of Kv1.3 inactivation : role of His399 / Somodi, S., Varga, Z., Hajdu, P., Starkus, J. G., Levy, D. I., Gaspar, R., Panyi, G.
Dátum:	2004
Megjegyzések:	The Kv1.3 K(+) channel lacks N-type inactivation, but during prolonged depolarized periods it inactivates via the slow (P/C type) mechanism. It bears a titratable histidine residue in position 399 (equivalent of Shaker 449), a site known to influence the rate of slow inactivation. As opposed to several other voltage-gated K(+) channels, slow inactivation of Kv1.3 is slowed when extracellular pH (pH(o)) is lowered under physiological conditions. Our findings are as follows. First, when His399 was mutated to a lysine, arginine, leucine, valine or tyrosine, extracellular acidification (pH 5.5) accelerated inactivation reminiscent of other Kv channels. Second, inactivation of the wild-type channel was accelerated by low pH(o) when the ionic strength of the external solution was raised. Inactivation of the H399K mutant was also accelerated by high ionic strength at pH 7.35 but not the inactivation of H399L. Third, after the external application of blocking barium ions, recovery of the wild-type current during washout was slower in low pH(o). Fourth, the dissociation rate of Ba(2+) was pH insensitive for both H399K and H399L. Furthermore, Ba(2+) dissociation rates were equal for H399K and the wild type at pH 5.5 and were equal for H399L and the wild type at pH 7.35. These observations support a model in which the electric field of the protonated histidines creates a potential barrier for potassium ions just outside the external mouth of the pore that hinders their exit from the binding site controlling inactivation. In Kv1.3, this effect overrides the generally observed speeding of slow inactivation when pH(o) is reduced.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Animals Barium Biophysics chemistry Extracellular Fluid genetics Histidine Human Humans Hungary Hydrogen-Ion Concentration Ion Channel Gating Kv1.3 Potassium Channel Lysine Membrane Potentials metabolism Models,Biological Mutation Patch-Clamp Techniques physiology Potassium Potassium Channels Potassium Channels,Voltage-Gated Research Support
Megjelenés:	American Journal of Physiology. Cell Physiology. - 287 : 4 (2004), p. C1067-C1076. -
További szerzők:	Varga Zoltán (1969-) (biofizikus, szakfordító) Hajdu Péter (1975-) (biofizikus) Starkus, John G. Levy, Daniel I. Gáspár Rezső (1944-) (biofizikus) Panyi György (1966-) (biofizikus)
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001-es BibID:	BIBFORM004739
Első szerző:	Starkus, John G.
Cím:	Mechanisms of the inhibition of Shaker potassium channels by protons / John G. Starkus, Zoltán Varga, Roland Schönherr, Stefan H. Heinemann
Dátum:	2003
ISSN:	0031-6768
Megjegyzések:	Potassium channels are regulated by protons in various ways and, in most cases, acidification results in potassium current reduction. To elucidate the mechanisms of proton-channel interactions we investigated N-terminally truncated Shaker potassium channels (Kv1 channels) expressed in Xenopus oocytes, varying pH at the intracellular and the extracellular face of the membrane. Intracellular acidification resulted in rapid and reversible channel block. The block was half-maximal at pH 6.48, thus even physiological excursions of intracellular pH will have an impact on K+ current. The block displayed only very weak voltage dependence and C-type inactivation and activation were not affected. Extracellular acidification (up to pH 4) did not block the channel, indicating that protons are effectively excluded from the selectivity filter. Channel current, however, was reduced greatly due to marked acceleration of C-type inactivation at low pH. In contrast, inactivation was not affected in the T449V mutant channel, in which C-type inactivation is impaired. The pH effect on inactivation of the wild-type channel had an apparent pK of 4.7, suggesting that protonation of extracellular acidic residues in Kv channels makes them subject to pH regulation
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Animals Comparative Study drug effects Female Ion Channel Gating Oocytes pharmacology physiology Potassium Potassium Channel Blockers Potassium Channels Protons Research Shaker Superfamily of Potassium Channels Support Xenopus
Megjelenés:	Pflügers Archiv. - 447 : 1 (2003), p. 44-54. -
További szerzők:	Varga Zoltán (1969-) (biofizikus, szakfordító) Schönherr, Roland Heinemann, Stefan H.
Internet cím:	Intézményi repozitóriumban (DEA) tárolt változat DOI
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001-es BibID:	BIBFORM004720
Első szerző:	Varga Zoltán (biofizikus, szakfordító)
Cím:	Cations affect the rate of gating charge recovery in wild-type and W434F Shaker channels through a variety of mechanisms / Varga, Z., Rayner, M. D., Starkus, J. G.
Dátum:	2002
Megjegyzések:	In this study we examine the effects of ionic conditions on the gating charge movement in the fast inactivation-removed wild-type Shaker channel and its W434F mutant. Our results show that various ionic conditions influence the rate at which gating charge returns during repolarization following a depolarizing pulse. These effects are realized through different mechanisms, which include the regulation of channel closing by occupying the cavity, the modulation of transitions into inactivated states, and effects on transitions between closed states via a direct interaction with the channel's gating charges. In generating these effects the cations act from the different binding sites within the pore. Ionic conditions, in which conducting wild-type channels close at different rates, do not significantly affect the rate of charge recovery upon repolarization. In these conditions, channel closing is fast enough not to be rate-limiting in the charge recovery process. In the permanently P-inactivated mutant channel, however, channel closing becomes the rate-limiting step, presumably due to weakened ion-ion interactions inside the pore and a slower intrinsic rate of gate closure. Thus, variations in closing rate induced by different ions are reflected as variations in the rate of charge recovery. In 115 mM internal Tris(+) and external K(+), Cs(+), or Rb(+), low inward permeation of these ions can be observed through the mutant channel. In these instances, channel closing becomes slower than in Tris(+)(O)//Tris(+)(I) solutions showing resemblance to the wild-type channel, where higher inward ionic fluxes also retard channel closing. Our data indicate that cations regulate the transition into the inactivated states from the external lock-in site and possibly the deep site. The direct action of barium on charge movement is probably exerted from the deep site, but this effect is not very significant for monovalent cations.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Binding Sites Research
Megjelenés:	The Journal of General Physiology. - 119 : 5 (2002), p. 467-485. -
További szerzők:	Rayner, Martin D. Starkus, John G.
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