title: Monovalent cationic channel activity in the inner membrane of nuclei from skeletal muscle fibers.
abstract: Nuclear ion channels remain among the least studied and biophysically characterized channels. Although considerable progress has been made in characterizing calcium release channels in the nuclear membrane, very little is known regarding the properties of nuclear monovalent cationic channels. Here, we describe a method to isolate nuclei from adult skeletal muscle fibers that are suitable for electrophysiological experiments. Using this approach, we show for the first time, to our knowledge, that a nuclear monovalent cationic channel (NMCC) is prominently expressed in the inner membrane of nuclei isolated from flexor digitorum brevis skeletal muscle fibers of adult mice. In isotonic 140 mM KCl, the skeletal muscle NMCC exhibits a unitary conductance of ?160 pS and high, voltage-independent open probability. Based on single-channel reversal potential measurements, NMCCs are slightly more permeable to potassium ions over sodium (PK/PNa = 2.68 ± 0.21) and cesium (PK/PCs = 1.39 ± 0.03) ions. In addition, NMCCs do not permeate divalent cations, are inhibited by calcium ions, and demonstrate weak rectification in asymmetric Ca(2+)-containing solutions. Together, these studies characterize a voltage-independent NMCC in skeletal muscle, the properties of which are ideally suited to serve as a countercurrent mechanism during calcium release from the nuclear envelope.
authors.affiliation: Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York. Electronic address: Viktor_Yarotskyy@URMC.Rochester.edu.
authors.forename: Viktor
authors.initials: V
authors.lastname: Yarotskyy
authors.affiliation: Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dirksen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002586:Cesium / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D007477:Ions / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D007473:Ion Channels; D007477:Ions; D002586:Cesium; D012964:Sodium; D011188:Potassium; D002118:Calcium