Antibody-guided photoablation of voltage-gated potassium currents. 2013

Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
Department of Physiology and Membrane Biology, University of California, Davis, Davis, CA 95616, USA. jsack@ucdavis.edu

A family of 40 mammalian voltage-gated potassium (Kv) channels control membrane excitability in electrically excitable cells. The contribution of individual Kv channel types to electrophysiological signaling has been difficult to assign, as few selective inhibitors exist for individual Kv subunits. Guided by the exquisite selectivity of immune system interactions, we find potential for antibody conjugates as selective Kv inhibitors. Here, functionally benign anti-Kv channel monoclonal antibodies (mAbs) were chemically modified to facilitate photoablation of K currents. Antibodies were conjugated to porphyrin compounds that upon photostimulation inflict localized oxidative damage. Anti-Kv4.2 mAb-porphyrin conjugates facilitated photoablation of Kv4.2 currents. The degree of K current ablation was dependent on photon dose and conjugate concentration. Kv channel photoablation was selective for Kv4.2 over Kv4.3 or Kv2.1, yielding specificity not present in existing neurotoxins or other Kv channel inhibitors. We conclude that antibody-porphyrin conjugates are capable of selective photoablation of Kv currents. These findings demonstrate that subtype-specific mAbs that in themselves do not modulate ion channel function are capable of delivering functional payloads to specific ion channel targets.

UI MeSH Term Description Entries
D008027 Light That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range. Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D011166 Porphyrins A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. Porphyrin
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051672 Shal Potassium Channels A shaker subfamily of potassium channels that participate in transient outward potassium currents by activating at subthreshold MEMBRANE POTENTIALS, inactivating rapidly, and recovering from inactivation quickly. KCND1 Potassium Channel,KCND2 Potassium Channel,KCND3 Potassium Channel,Kv4 Potassium Channels,Kv4.1 Potassium Channel,Kv4.2 Potassium Channel,Kv4.3 Potassium Channel,Kv4.3L Potassium Channel,Potassium Channel, KCND1,Potassium Channel, KCND2,Potassium Channel, KCND3,Potassium Channel, Kv4.1,Potassium Channel, Kv4.2,Potassium Channel, Kv4.3,Potassium Channel, Kv4.3L,Potassium Channels, Kv4,Potassium Channels, Shal
D026902 Potassium Channel Blockers A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS. Channel Blockers, Potassium,Potassium Channel Blocker,Blocker, Potassium Channel,Blockers, Potassium Channel,Channel Blocker, Potassium

Related Publications

Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
June 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
December 2016, Circulation research,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
November 2010, Neurologic clinics,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
July 1993, Journal of neurophysiology,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
July 2014, Age and ageing,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
January 2005, Cell biochemistry and biophysics,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
January 1999, The Journal of general physiology,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
August 2012, Indian journal of experimental biology,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
June 2002, Brain research,
Jon T Sack, and Nicholas Stephanopoulos, and Daniel C Austin, and Matthew B Francis, and James S Trimmer
June 2003, Pflugers Archiv : European journal of physiology,
Copied contents to your clipboard!