TRPC (transient receptor potential, canonical) is a family of ion channels that mediate changes in plasma membrane (PM) cation permeability induced by stimulation of phospholipase C (PLC). PLC is a cellular integrator that receives input from G protein coupled receptors (GPCR) and from receptor tyrosine kinases (RTK). A central cellular function of TRPC channels is to regulate Ca2+ influx across the PM induced by stimulation of these receptors by hormones, neurotransmitters, and growth factors. Specific TRPC channels may also be activated by other means such as membrane stretch and changes in cell volume. Physiological, biochemical, and molecular studies revealed that TRPC channel activity is regulated by their interaction with many auxiliary proteins. Although many channels contain functional subunits, TRPC channels are unique in that their activity is modulated rather than enabled by the auxiliary proteins. Such context dependence of TRPC channel activity necessitates the development of tools that enable enumeration and exploration of the TRPC channel auxiliary proteins and their roles in the channel function. This chapter focuses on these tools and on the results and conclusions made possible because of the use of these tools.
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