title: Time- and voltage-dependent components of Kv4.3 inactivation.
abstract: Kv4.3 inactivation is a complex multiexponential process, which can occur from both closed and open states. The fast component of inactivation is modulated by the N-terminus, but the mechanisms mediating the other components of inactivation are controversial. We studied inactivation of Kv4.3 expressed in Xenopus laevis oocytes, using the two-electrode voltage-clamp technique. Inactivation during 2000 ms pulses at potentials positive to the activation threshold was described by three exponents (46 +/- 3, 152 +/- 13, and 930 +/- 50 ms at +50 mV, n = 7) whereas closed-state inactivation (at potentials below threshold) was described by two exponents (1079 +/- 119 and 3719 +/- 307 ms at -40 mV, n = 9). The fast component of open-state inactivation was dominant at potentials positive to -20 mV. Negative to -30 mV, the intermediate and slow components dominated inactivation. Inactivation properties were dependent on pulse duration. Recovery from inactivation was strongly dependent on voltage and pulse duration. We developed an 11-state Markov model of Kv4.3 gating that incorporated a direct transition from the open-inactivated state to the closed-inactivated state. Simulations with this model reproduced open- and closed-state inactivation, isochronal inactivation relationships, and reopening currents. Our data suggest that inactivation can proceed primarily from the open state and that multiple inactivation components can be identified.
authors.affiliation: Department of Physiology and Biophysics, University at Buffalo, The State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Wang
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Bondarenko
authors.forename: Yu-jie
authors.initials: YJ
authors.lastname: Qu
authors.forename: Glenna C L
authors.initials: GC
authors.lastname: Bett
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morales
authors.forename: Randall L
authors.initials: RL
authors.lastname: Rasmusson
authors.forename: Harold C
authors.initials: HC
authors.lastname: Strauss
mesh_terms: D000818:Animals; D019295:Computational Biology; D003198:Computer Simulation; D018076:DNA, Complementary / Q000378:metabolism; D004594:Electrophysiology; D005260:Female; D007700:Kinetics; D008390:Markov Chains; D008954:Models, Biological; D008956:Models, Chemical; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051672:Shal Potassium Channels / Q000737:chemistry / Q000502:physiology*; D012984:Software; D013997:Time Factors; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D018076:DNA, Complementary; D051672:Shal Potassium Channels