Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry

Naomi Kunichika, Ying Yu, Carmelle V. Remillard, Oleksandr Platoshyn, Shen Zhang, Jason Yuan

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Transient receptor potential (TRP) cation channels are a critical pathway for Ca2+ entry during pulmonary artery (PA) smooth muscle contraction. However, whether canonical TRP (TRPC) subunits and which TRP channel isoforms are involved in store depletion-induced pulmonary vasoconstriction in vivo remain unclear. This study was designed to test whether overexpression of the human TRPC1 gene (hTRPC1) in rat PA enhances pulmonary vasoconstriction due to store depletion-mediated Ca2+ influx. The hTRPC1 was infected into rat PA rings with an adenoviral vector. RT-PCR and Western blot analyses confirmed the mRNA and protein expression of hTRPC1 in the arterial rings. The amplitude of active tension induced by 40 mM K+ (40K) in PA rings infected with an empty adenoviral vector (647 ± 88 mg/mg) was similar to that in PA rings infected with hTRPC1 (703 ± 123 mg/mg, P = 0.3). However, the active tension due to capacitative Ca2+ entry (CCE) induced by cyclopiazonic acid was significantly enhanced in PA rings overexpressing hTRPC1 (91 ± 13% of 40K-induced contraction) compared with rings infected with an empty adenoviral vector (61 ± 14%, P < 0.001). Endothelial expression of hTRPC1 was not involved since the CCE-induced vasoconstriction was also enhanced in endothelium-denuded PA rings infected with the adenoviral vector carrying hTRPC1. These observations demonstrate that hTRPC1 is an important Ca2+-permeable channel that mediates pulmonary vasoconstriction when PA smooth muscle cell intracellular Ca2+ stores are depleted.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume287
Issue number5 31-5
DOIs
StatePublished - Nov 2004
Externally publishedYes

Fingerprint

Vasoconstriction
Pulmonary Artery
Lung
Genes
Transient Receptor Potential Channels
Critical Pathways
Muscle Contraction
Smooth Muscle Myocytes
Endothelium
Smooth Muscle
Protein Isoforms
Western Blotting
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Calcium
  • Capacitative calcium entry
  • Transient receptor potential cation channels

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry. / Kunichika, Naomi; Yu, Ying; Remillard, Carmelle V.; Platoshyn, Oleksandr; Zhang, Shen; Yuan, Jason.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 287, No. 5 31-5, 11.2004.

Research output: Contribution to journalArticle

Kunichika, Naomi ; Yu, Ying ; Remillard, Carmelle V. ; Platoshyn, Oleksandr ; Zhang, Shen ; Yuan, Jason. / Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2004 ; Vol. 287, No. 5 31-5.
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