[Frontiers in Bioscience 14, 45-58, January 1, 2009]
The integrative function of TRPC channels

Kirill Kiselyov1, Randen L Patterson2

1 Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, 2 Department of Biology, The Pennsylvania State University, University Park, PA


1. Abstract
2. Native TRPC
3. TRPC channels in Mammalian Physiology
4. Activation mechanisms of TRPC channels
4.1. Diacylglycerol
4.2. Activation in Response to Ca2+ store depletion.
4.3. Mechanosensation
5. TRPC modulation
5.1. Covalent Modifications
5.1.1. Phosphorylation Protein Kinase C Protein Kinase G Src-family tyrosine kinases
5.1.2. Nitrosylation
5.1.3. Glycosylation
5.2. Lipids
5.2.1. PIP2 and PIP3
5.2.2. Lysophosphatidic Choline and Sphingosine-1-Phosphate
5.2.3. Cholesterol
5.3. Interaction with auxiliary proteins.
5.3.1. Homer/IP3R
5.3.2. Calmodulin
5.3.3. Junctate
6. TRPothesizing
7. Summary
8. References


TRPC is a subfamily of Transient Receptor Potential channels that have the highest degree of homology to the Drosophila photoreceptors' TRP. TRPC open in response to stimulation of plasma membrane receptors that activate phospholipase C, triggering transmembrane Ca2+ influx. TRPC activity has been directly implicated in regulation of vascular tone, kidney filtration, acrosomal reaction and pheromone recognition. As humans contain six TRPC channels, which form homo- and hetero-tetramers, TRPCs are capable of forming multiple channels of varying current/voltage relationships and activation properties. This allows TRPC to participate in an array of intercellular pathways induced by chemical mediators including hormones, neurotransmitters and growth factors. The strength of TRPC response to stimulation is modulated by several factors such as covalent modification, interaction with auxiliary proteins and changes in the lipid environment. The existence of several modulatory inputs that converge on TRPC enables integration of various stimuli and differentiation of Ca2+ signaling in specific tissues. This synthesizes the current literature describing the known functions and phenomenology associated with TRPC channels, with a specific focus on the activation and modulatory mechanisms. We suggest that the polymodal regulation of TRPC channels is likely to explain many specific aspects of TRPC behavior in different tissues.