Functional ion channels in human pulmonary artery smooth muscle cells: Voltage-dependent cation channels

Amy L. Firth, Carmelle V. Remillard, Oleksandr Platoshyn, Ivana Fantozzi, Eun A. Ko, Jason X.J. Yuan

Research output: Contribution to journalReview article

53 Scopus citations

Abstract

The activity of voltage-gated ion channels is critical for the maintenance of cellular membrane potential and generation of action potentials. In turn, membrane potential regulates cellular ion homeostasis, triggering the opening and closing of ion channels in the plasma membrane and, thus, enabling ion transport across the membrane. Such transmembrane ion fluxes are important for excitation-contraction coupling in pulmonary artery smooth muscle cells (PASMC). Families of voltage-dependent cation channels known to be present in PASMC include voltage-gated K+ (Kv) channels, voltage-dependent Ca2+-activated K+ (Kca) channels, L-and T-type voltage-dependent Ca2+ channels, voltage-gated Na+ channels and voltage-gated proton channels. When cells are dialyzed with Ca2+-free K+-solutions, depolarization elicits four components of 4-aminopyridine (4-AP)-sensitive Kvcurrents based on the kinetics of current activation and inactivation. In cell-attached membrane patches, depolarization elicits a wide range of single-channel K+ currents, with conductances ranging between 6 and 290 pS. Macroscopic 4-AP-sensitive Kv currents and iberiotoxin-sensitive Kca currents are also observed. Transcripts of (a) two Na+ channel α-subunit genes (SCN5A and SCN6A), (b) six Ca2+ channel α−subunit genes (α1A, α, α, α1D, α1E and α1G) and many regulatory subunits (α2δ1, β1-4, and γ6), (c) 22 Kv channel α−subunit genes (Kv1.1-Kv1.7, Kv1.10, Kv2.1, Kv3.1, Kv3.3, Kv3.4, Kv4.1, Kv4.2, Kv5.1, Kv 6.1-Kv6.3, Kv9.1, Kv9.3, Kv10.1 and Kv11.1) and three Kv channel β-subunit genes (Kvβ1-3) and (d) four Kca channel α−subunit genes (Sloα1 and SK2-SK4) and four Kca channel β-subunit genes (Kcaβ1-4) have been detected in PASMC. Tetrodotoxin-sensitive and rapidly inactivating Na+ currents have been recorded with properties similar to those in cardiac myocytes. In the presence of 20 mM external Ca2+, membrane depolarization from a holding potential of-100 mV elicits a rapidly inactivating T-type Ca2+ current, while depolarization from a holding potential of-70 mV elicits a slowly inactivating dihydropyridine-sensitive L-type Ca2+ current. This review will focus on describing the electrophysiological properties and molecular identities of these voltage-dependent cation channels in PASMC and their contribution to the regulation of pulmonary vascular function and its potential role in the pathogenesis of pulmonary vascular disease.

Original languageEnglish (US)
Pages (from-to)48-71
Number of pages24
JournalPulmonary Circulation
Volume1
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Ca channel
  • K channel
  • Membrane potential
  • Na channel
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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