Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
Ion channels are membrane-spanning proteins that allow ions to permeate at high rates. The kinetic characteristics of the channels present in a cell determine the cell signaling profile and therefore cell function in many different physiological processes. We found that Kv1.7 channels from mouse heart muscle have two putative translation initiation start sites that generate two channel isoforms with different functional characteristics, mKv1.7L (489 aa) and a shorter mKv1.7S (457 aa). The electrophysiological analysis of mKv1.7L and mKv1.7S channels revealed that the two channel isoforms have different inactivation kinetics. The channel resulting from the longer protein (L) inactivates faster than the shorter channels (S). Our data supports the hypothesis that mKv1.7L channels inactivate predominantly due to an N-type related mechanism, which is impaired in the mKv1.7S form. Furthermore, only the longer version mKv1.7L is regulated by the cell redox state, whereas the shorter form mKv1.7S is not. Thus, expression starting at each translation initiation site results in significant functional divergence. Our data suggest that the redox modulation of mKv1.7L may occur through a site in the cytoplasmic N-terminal domain that seems to encompass a metal coordination motif resembling those found in many redox-sensitive proteins. The mRNA expression profile and redox modulation of mKv1.7 kinetics identify these channels as molecular entities of potential importance in cellular redox-stress states such as hypoxia.
Finol-Urdaneta
Rocio K
RK
Max-Planck-Institute for Experimental Medicine, Group of Molecular and Cellular Neuropharmacology, Göttingen, Germany.
Strüver
Nina
N
Terlau
Heinrich
H
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004220:Disulfides / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D011188:Potassium / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D018075:RNA, Complementary / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D051637:Shaker Superfamily of Potassium Channels / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
D004220:Disulfides; C513961:Kv1.7 potassium channel, mouse; D020033:Protein Isoforms; D018075:RNA, Complementary; D051637:Shaker Superfamily of Potassium Channels; D011188:Potassium; D004229:Dithiothreitol