Activation, subunit composition and physiological relevance of DAG-sensitive TRPC proteins

Area of Science:

• Molecular biology
• Cell physiology
• Cardiovascular research

Background:

• The Transient Receptor Potential (TRP) protein family comprises seven members with a shared gating mechanism involving phospholipase C.
• Some TRP channels activate after intracellular calcium store depletion, while others respond to lipid messengers.
• TRPC3, TRPC6, and TRPC7 form a subfamily sensitive to diacylglycerols (DAGs).

Purpose of the Study:

• To investigate the function and activation mechanism of TRPC6 channels.
• To determine the role of TRPC6 in smooth muscle cells and its potential involvement in vasoconstriction.

Main Methods:

• Analysis of TRPC6 channel activation by diacylglycerols (DAGs).
• Assessment of TRPC6 expression in smooth muscle cells.
• Measurement of DAG-evoked calcium transients in myocytes.

Main Results:

• TRPC6 channels are activated by DAG in a membrane-delimited manner, independent of protein kinase C.
• Internal calcium store depletion is not necessary for TRPC6 activation.
• TRPC6 is highly expressed in smooth muscle cells, and DAG stimulation causes calcium transients in myocytes from lung and blood vessels.

Conclusions:

• TRPC6 is a strong candidate for non-selective cation channels in smooth muscle cells.
• TRPC6 channels may play a role in vasoconstrictor-activated cation influx and myogenic tone in resistance arteries.
• Understanding TRPC protein heteromultimerization is crucial for elucidating their physiological functions.