title: Identification of functional voltage-gated Na(+) channels in cultured human pulmonary artery smooth muscle cells.
abstract: Electrical excitability, which plays an important role in excitation-contraction coupling in the pulmonary vasculature, is regulated by transmembrane ion flux in pulmonary artery smooth muscle cells (PASMC). This study aimed to characterize the electrophysiological properties and molecular identities of voltage-gated Na(+) channels in cultured human PASMC. We recorded tetrodotoxin (TTX) sensitive and rapidly inactivating Na(+) currents with properties similar to those described in cardiac myocytes. Using RT-PCR, we detected transcripts of seven Na(+) channel alpha genes (SCN2A, 3A, 4A, 7A, 8A, 9A, and 11A), and two beta subunit genes (SCN1B and 2B). Our results demonstrate that human PASMC express TTX-sensitive voltage-gated Na(+) channels. Their physiological functions remain unresolved, although our data suggest that Na(+) channel activity does not directly influence membrane potential, intracellular Ca(2+) release, or proliferation in normal human PASMC. Whether their expression and/or activity are heightened in the pathological state is discussed.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0725.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Platoshyn
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0725.
authors.forename: Carmelle V
authors.initials: CV
authors.lastname: Remillard
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0725.
authors.forename: Ivana
authors.initials: I
authors.lastname: Fantozzi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0725.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Sison
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0725.
authors.forename: Jason X-J
authors.initials: JX
authors.lastname: Yuan
mesh_terms: D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D008536:Meglumine / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; D061566:Voltage-Gated Sodium Channels
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D062552:NAV1.3 Voltage-Gated Sodium Channel; D062553:NAV1.4 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C491886:SCN11A protein, human; C470379:SCN1B protein, human; C568251:SCN2A protein, human; C117620:SCN2B protein, human; C424715:SCN3A protein, human; C106251:SCN4A protein, human; C503482:SCN7A protein, human; C100681:SCN8A protein, human; C486866:SCN9A protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit; D062548:Voltage-Gated Sodium Channel beta-2 Subunit; D061566:Voltage-Gated Sodium Channels; D002586:Cesium; D013779:Tetrodotoxin; D008536:Meglumine