Multiple modes of a-type potassium current regulation.
Voltage-dependent potassium (K+) channels (Kv) regulate cell excitability by controlling the movement of K+ ions across the membrane in response to changes in the cell voltage. The Kv family, which includes A-type channels, constitute the largest group of K+ channel genes within the superfamily of Na+, Ca2+ and K+ voltage-gated channels. The name "A-type" stems from the typical profile of these currents that results form the opposing effects of fast activation and inactivation. In neuronal cells, A-type currents (I(A)), determine the interval between two consecutive action potentials during repetitive firing. In cardiac muscle, A-type currents (I(to)), control the initial repolarization of the myocardium. Structurally, A-type channels are tetramers of alpha-subunits each containing six putative transmembrane domains including a voltage-sensor. A-type channels can be modulated by means of protein-protein interactions with so-called beta-subunits that control inactivation voltage sensitivity and other properties, and by post-transcriptional modifications such as phosphorylation or oxidation. Recently a new mode of A-type regulation has been discovered in the form of a class of hybrid beta-subunits that posses their own enzymatic activity. Here, we review the biophysical and physiological properties of these multiple modes of A-type channel regulation.
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Physiology and Biophysics, 683 Hoes Lane, Piscataway, NJ 08854, USA.
Shi-Qing
SQ
Cai
Wenchao
W
Li
Federico
F
Sesti
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology
D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D011188:Potassium