Heteromeric assembly of Kv2.1 with Kv9.3: effect on the state dependence of inactivation.
Modulatory alpha-subunits of Kv channels remain electrically silent after homomeric expression. Their interactions with Kv2 alpha-subunits via the amino-terminal domain promote the assembly of heteromeric functional channels. The kinetic features of these heteromers differ from those of Kv2 homomers, suggesting a distinct role in electrical signaling. This study investigates biophysical properties of channels emerging from the coexpression of Kv2.1 with the modulatory alpha-subunit Kv9.3. Changes relative to homomeric Kv2.1 concern activation, deactivation, inactivation, and recovery from inactivation. A detailed description of Kv2.1/Kv9.3 inactivation is presented. Kv2.1/Kv9.3 heteromers inactivate in a fast and complete fashion from intermediate closed states, but in a slow and incomplete manner from open states. Intermediate closed states of channel gating can be approached through partial activation or deactivation, according to a proposed qualitative model. These transitions are rate-limiting for Kv2.1/Kv9.3 inactivation. Finally, based on the kinetic description, we propose a putative function for Kv2.1/Kv9.3 heteromers in rat heart.
Kerschensteiner
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Molekulare Biologie Neuronaler Signale, Max-Planck-Institut für Experimentelle Medizin, D-37075 Göttingen, Germany.
Stocker
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M
D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D051668:Delayed Rectifier Potassium Channels; D015870:Gene Expression; D007700:Kinetics; D008564:Membrane Potentials; D008845:Microinjections; D009206:Myocardium / Q000737:chemistry; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011487:Protein Conformation; D018075:RNA, Complementary / Q000235:genetics; D051381:Rats; D051669:Shab Potassium Channels; D014981:Xenopus
D018076:DNA, Complementary; D051668:Delayed Rectifier Potassium Channels; C496991:Kcnb1 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018075:RNA, Complementary; D051669:Shab Potassium Channels; D011188:Potassium