Novel KChIP2 isoforms increase functional diversity of transient outward potassium currents.
Kv4.3 channels conduct transient outward K(+) currents in the human heart and brain where they mediate the early phase of action potential repolarization. KChIP2 proteins are members of a new class of calcium sensors that modulate the surface expression and biophysical properties of Kv4 K(+) channels. Here we describe three novel isoforms of KChIP2 with an alternatively spliced C-terminus (KChIP2e, KChIP2f) or N-terminus (KChIP2g). KChIP2e and KChIP2f are expressed in the human atrium, whereas KChIP2g is predominantly expressed in the brain. The KChIP2 isoforms were coexpressed with Kv4.3 channels in Xenopus oocytes and currents recorded with two-microelectrode voltage-clamp techniques. KChIP2e caused a reduction in current amplitude, an acceleration of inactivation and a slowing of the recovery from inactivation of Kv4.3 currents. KChIP2f increased the current amplitude and slowed the rate of inactivation, but did not alter the recovery from inactivation or the voltage of half-maximal inactivation of Kv4.3 channels. KChIP2g increased current amplitudes, slowed the rate of inactivation and shifted the voltage of half-maximal inactivation to more negative potentials. The biophysical changes induced by these alternatively spliced KChIP2 proteins differ markedly from previously described KChIP2 proteins and would be expected to increase the diversity of native transient outward K(+) currents.
Decher
Niels
N
Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 N 2000 E, Salt Lake City, UT 84112, USA. niels.decher@gmx.net
Barth
Andreas S
AS
Gonzalez
Teresa
T
Steinmeyer
Klaus
K
Sanguinetti
Michael C
MC
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004558:Electric Stimulation; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating; D007536:Isomerism; D051605:Kv Channel-Interacting Proteins; D008163:Luminescent Measurements; D008564:Membrane Potentials / Q000502:physiology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels; D014982:Xenopus laevis
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; C497021:KCND3 protein, human; C496752:KCNIP2 protein, human; D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051672:Shal Potassium Channels