Upregulated TRP and enhanced capacitative Ca(2+) entry in human pulmonary artery myocytes during proliferation

Am J Physiol Heart Circ Physiol. 2001 Feb;280(2):H746-55. doi: 10.1152/ajpheart.2001.280.2.H746.

Abstract

A rise in cytosolic Ca(2+) concentration ([Ca(2+)](cyt)) due to Ca(2+) release from intracellular Ca(2+) stores and Ca(2+) influx through plasmalemmal Ca(2+) channels plays a critical role in mitogen-mediated cell growth. Depletion of intracellular Ca(2+) stores triggers capacitative Ca(2+) entry (CCE), a mechanism involved in maintaining Ca(2+) influx and refilling intracellular Ca(2+) stores. Transient receptor potential (TRP) genes have been demonstrated to encode the store-operated Ca(2+) channels that are activated by Ca(2+) store depletion. In this study, we examined whether CCE, activity of store-operated Ca(2+) channels, and human TRP1 (hTRP1) expression are essential in human pulmonary arterial smooth muscle cell (PASMC) proliferation. Chelation of extracellular Ca(2+) and depletion of intracellularly stored Ca(2+) inhibited PASMC growth in media containing serum and growth factors. Resting [Ca(2+)](cyt) as well as the increases in [Ca(2+)](cyt) due to Ca(2+) release and CCE were all significantly greater in proliferating PASMC than in growth-arrested cells. Consistently, whole cell inward currents activated by depletion of intracellular Ca(2+) stores and the mRNA level of hTRP1 were much greater in proliferating PASMC than in growth-arrested cells. These results suggest that elevated [Ca(2+)](cyt) and intracellularly stored [Ca(2+)] play an important role in pulmonary vascular smooth muscle cell growth. CCE, potentially via hTRP1-encoded Ca(2+)-permeable channels, may be an important mechanism required to maintain the elevated [Ca(2+)](cyt) and stored [Ca(2+)] in human PASMC during proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blood Proteins / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Channels, L-Type / metabolism
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cells, Cultured
  • Gene Expression / physiology
  • Humans
  • Hypertension, Pulmonary / metabolism
  • Imidazoles / pharmacology
  • Indoles / pharmacology
  • Membrane Potentials / physiology
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism*
  • Nickel / pharmacology
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques
  • Pulmonary Artery / cytology*
  • Pulmonary Artery / metabolism*
  • RNA, Messenger / analysis
  • TRPC Cation Channels
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • Vasodilator Agents / pharmacology

Substances

  • Blood Proteins
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Imidazoles
  • Indoles
  • RNA, Messenger
  • TRPC Cation Channels
  • Vasodilator Agents
  • transient receptor potential cation channel, subfamily C, member 1
  • Nickel
  • 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
  • Nifedipine
  • Calcium
  • cyclopiazonic acid