ABSTRACT
Acknowledgments ................................................................................................ 157
References............................................................................................................. 157
Many cells including exocrine gland cells and vascular smooth muscle cells show a
coordinated regulation of an intracellular Ca2þ-release mechanism and the entry of Ca2þ across the plasma membrane. This Ca2þ entry is the basis for sustained [Ca2þ]i elevations that are important for various cellular functions including gene expression, secretion, and cell proliferation [1]. A link between Ca2þ release and Ca2þ entry into cells was proposed by Putney [2]. His model described an initial emptying of the intracellular Ca2þ stores by inositol 1,4,5-trisphosphate (IP3), followed by entry of Ca2þ into the cytosol, and refilling of the stores. This type of Ca2þ entry is referred to as capacitative or store-operated Ca2þ-entry. The first electrical measurement of current through a store-operated channel (SOC) was
achieved in mast cells and this current was termed Ca2þ-release activated Ca2þ
channel (CRAC) current [3]. The desire to identify the molecular nature of this SOC
was and still is the motivation for many workers to characterize mammalian TRP
channels. As it turned out, the activation of some of these TRP channels is linked to
PLC activation; but most unanticipated is that the activation of other TRPs is due
to a medley of novel regulatory mechanisms that appear to be independent of PLC
signaling. These include activation by temperature, cell swelling, noxious and
mechanical stimuli, and by binding of ligands such as anandamide, arachidonic
acid derivates, protons, menthol, icilin, capsaicin, and phorbol esters. A number of
comprehensive reviews have been published on these issues recently [4-6], and in
this chapter we will discuss some of the problems that show up when cloning the
cDNAs of ‘‘new’’ TRPs and elaborate on problems envisioned when studying TRP
protein expression by antibodies.