Properties, expression and potential roles of cardiac K+ channel accessory subunits: MinK, MiRPs, KChIP, and KChAP.
Over the past 10 years, cDNAs encoding a wide range of pore-forming K(+)-channel alpha-subunits have been cloned and found to result in currents with many properties of endogenous cardiac K(+) channels upon homomeric expression in heterologous systems. However, a variety of remaining discrepancies have led to a search for other subunits that might be involved in the formation of native channels. Over the past few years, a series of accessory subunits has been discovered that modify current properties upon coexpression with alpha-subunits. One of these, the minimal K(+)-channel subunit minK, is essential for formation of the cardiac slow delayed-rectifier K(+) current, I(Ks), and may also interact in functionally important ways with other alpha-subunits. Another, the K(+)-channel interacting protein KChIP appears critical in formation of native transient outward current (I(to)) channels. The roles of 2 other accessory subunits, the minK-related peptide MiRP and the K(+)-channel accessory protein, KChAP, remain unclear. This article reviews the available knowledge regarding the accessory subunits minK, MiRP, KChIP and KChAP, dealing with their structure, effects on currents carried by coexpressed alpha-subunits, expression in cardiac tissues and potential physiological function. On the basis of the available information, we attempt to assess the potential involvement of these accessory K(+)-channel subunits in cardiac pathophysiology and in developing new therapeutic approaches.
D000595:Amino Acid Sequence; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D006329:Heart Conduction System / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000889:Anti-Arrhythmia Agents; D015221:Potassium Channels; D021122:Protein Subunits; D011188:Potassium