Focus on TRP channels in cystic fibrosis

Chloé Grebert, Frederic Becq, Clarisse Vandebrouck

Cell Calcium 81 (2019) 29-37

A B S T R A C T

The Transient Receptor Potential (TRP) protein superfamily is a group of cation channels expressed in various
cell types and involved in respiratory diseases such as cystic fibrosis (CF), the genetic disease caused by CF
Transmembrane conductance Regulator (CFTR) mutations. In human airway epithelial cells, there is growing
evidence for a functional link between CFTR and TRP channels. TRP channels contribute to transmitting extracellular
signals into the cells and, in an indirect manner, to CFTR activity via a Ca2+ rise signaling. Indeed,
mutated CFTR-epithelial cells are characterized by an increased Ca2+ influx and, on the opposite, by a decreased
of magnesium influx, both being mediated by TRP channels. This increasing cellular Ca2+ triggers the activation
of calcium-activated chloride channels (CaCC) or CFTR itself, via adenylyl cyclase, PKA and tyrosine kinases
activation, but also leads to an exaltation of the inflammatory response. Another shortcoming in mutated CFTRepithelial
cells is a [Mg2+]i decrease, associated with impaired TRPM7 functioning. This deregulation has to be
taken into consideration in CF physiopathology, as Mg2+ is required for ATP hydrolysis and CFTR activity. The
modulation of druggable TRP channels could supplement CF therapy either an anti-inflammatory drug or for
CFTR potentiation, according to the balance between exacerbation and respite phases. The present paper focus
on TRPA1, TRPC6, TRPM7, TRPV2, TRPV4, TRPV6 and ORAI 1, the proteins identified, for now, as dysfunctional
channels, in CF cells.

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