TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca2+ to trigger exocytosis in neuroendocrine cells

Alexander Obukhov, Martha C. Nowycky

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Transient receptor potential (TRP) channels form a large family of plasma membrane cation channels. Mammalian members of the "short" TRP family (TRP channel (TRPC) 1-7 are Ca2+-permeant, non-selective cation channels that are widely expressed in various cell types, including neurons. TRPC activity is linked through unknown mechanisms to G-protein-coupled receptors or receptor tyrosine kinases that activate phospholipase C. To investigate the properties and function of TRPC4 in neuronally derived cells, we transiently expressed mouse TRPC4 and histamine H1 receptor in mouse adrenal chromaffin cells and PC12 cells. Histamine, but not thapsigargin, stimulated Mn2+ influx in transfected cells. In the whole-cell patch clamp mode, histamine triggered a transient current in TRPC4-expressing cells. No current was evoked by perfusion with inositol 1,4,5-trisphosphate. When exocytosis was monitored with the capacitance detection technique, the magnitude of the membrane capacitance increase (ΔCm) on application of histamine in H1 receptor/TRPC4-expressing chromaffin cells was comparable with that triggered by a train of depolarizing pulses. Our results indicate that TRPC4 channels behave as receptor, but not store-operated, channels in neuronally derived cells. TRPC4 channels can provide sufficient Ca2+ influx to trigger a robust secretory response in voltage-clamped neurosecretory cells. Similar mechanisms may modulate exocytosis in other neuronal systems.

Original languageEnglish (US)
Pages (from-to)16172-16178
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number18
DOIs
StatePublished - May 3 2002
Externally publishedYes

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Neuroendocrine Cells
Exocytosis
G-Protein-Coupled Receptors
Histamine
Transient Receptor Potential Channels
Histamine H1 Receptors
Cations
Capacitance
Inositol 1,4,5-Trisphosphate
Thapsigargin
Clamping devices
Receptor Protein-Tyrosine Kinases
Type C Phospholipases
Chromaffin Cells
Cell membranes
Neurons
Membranes
Electric potential
PC12 Cells
Ion Channels

ASJC Scopus subject areas

  • Biochemistry

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TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca2+ to trigger exocytosis in neuroendocrine cells. / Obukhov, Alexander; Nowycky, Martha C.

In: Journal of Biological Chemistry, Vol. 277, No. 18, 03.05.2002, p. 16172-16178.

Research output: Contribution to journalArticle

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