Apoptosis recruits two-pore domain potassium channels used for homeostatic volume regulation

• Published in: American Journal of Physiology: Cell Physiology 2002-03, Vol.282 (3), p.C588-C594
• Main Authors: Trimarchi, James R, Liu, Lin, Smith, Peter J. S, Keefe, David L
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Cell Size - physiology; Cells, Cultured; Cytochalasin D - pharmacology; Electrophysiology; Female; Homeostasis - physiology; Hydrogen Peroxide - pharmacology; Male; Mercuric Chloride - pharmacology; Mice; Muscle Relaxants, Central - pharmacology; Nucleic Acid Synthesis Inhibitors - pharmacology; Oxidants - pharmacology; Potassium - metabolism; Potassium Channel Blockers; Potassium Channels - agonists; Potassium Channels - metabolism; Quinine - pharmacology; Tetradecanoylphorbol Acetate - pharmacology; Zygote - drug effects; Zygote - metabolism
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00365.2001

1  Laboratory for Reproductive Medicine and 2  BioCurrents Research Center, Marine Biological Laboratory, Woods Hole, Massachusetts 02543; and 3  Women and Infants Hospital, Brown University, Providence, Rhode Island 02905 Cell shrinkage is an incipient hallmark of apoptosis and is accompanied by potassium release that decreases the concentration of intracellular potassium and regulates apoptotic progression. The plasma membrane K + channel recruited during apoptosis has not been characterized despite its importance as a potential therapeutic target. Here we provide evidence that two-pore domain K + (K 2P ) channels underlie K + efflux during apoptotic volume decreases (AVD) in mouse embryos. These K 2P channels are inhibited by quinine but are not blocked by an array of pharmacological agents that antagonize other K + channels. The K 2P channels are uniquely suited to participate in the early phases of apoptosis because they are not modulated by common intracellular messengers such as calcium, ATP, and arachidonic acid, transmembrane voltage, or the cytoskeleton. A K + channel with similar biophysical properties coordinates regulatory volume decreases (RVD) triggered by changing osmotic conditions. We propose that K 2P channels are the pathway by which K + effluxes during AVD and RVD and that apoptosis co-opts mechanisms more routinely employed for homeostatic cell volume regulation. self-referencing electrode; cell volume; quinine; cell shrinkage