TRP: Its Role in Phototransduction and Store-Operated Ca2+ Entry

Perhaps the best characterized SOC is the CRAC (Ca2+-release activated Ca2+) channel described in several cell types, including mast cells (Hoth and Penner 1992xHoth, M and Penner, R. Nature. 1992; 355: 353–356Crossref | PubMed | Scopus (1131)See all ReferencesHoth and Penner 1992) and T lymphocytes (Zweifach and Lewis 1993xZweifach, A and Lewis, R.S. Proc. Natl. Acad. Sci. USA. 1993; 90: 6295–6299Crossref | PubMedSee all ReferencesZweifach and Lewis 1993). It is highly selective for Ca2+ (PCa/PNa ∼ 1000), has a small unitary conductance (∼24 fS in 110 mM Ca2+) and exhibits gating kinetics that depend on Ca2+ (Lewis et al. 1996xSee all ReferencesLewis et al. 1996). Another SOC described in A431 cells is selective for Ba2+ over Ca2+ and exhibits a higher unitary conductance (2 pS in the presence of 200 mM Ca2+) (Clapham 1995xClapham, D.E. Cell. 1995; 80: 259–268Abstract | Full Text PDF | PubMed | Scopus (1958)See all ReferencesClapham 1995). What is the relationship between these channels and TRP? Although detailed biophysical information is not available for TRP due to the difficulty of measuring currents across the microvillar membrane, differences in Ca2+ selectivity alone would suggest that if trp encodes a channel, it is probably different from the CRAC channel. SOCs may be members of a broad family of ion channels with different permeation properties and sensitivity to stimulation; differences between TRP and TRPL illustrate the potential for functional diversity within this putative ion-channel family. If TRP and TRPL function as ion channels, it will be important to understand their subunit organization, in particular whether they form homomeric or heteromeric channels.With respect to the role of TRP in Drosophila photoreception, there are several possibilities. TRP could act as a SOC opened by a drop in intraluminal free Ca2+ concentration during phototransduction. This leads to at least two predictions: first, that light stimulation should release Ca2+ from internal stores, and second that depletion of stores should increase membrane conductance. Recent reports suggest that neither holds true: light-induced currents can be elicited in the absence of external Ca2+ without a rise in [Ca2+]i, and thapsigargin releases intracellular Ca2+ without stimulating a LIC (15xRanganathan, R, Malicki, D.M, and Zuker, C.S. Ann. Rev. Neurosci. 1995; 18: 283–317Crossref | PubMedSee all References, 6xHardie, R.C. J. Neurosci. 1996; 16: 2924–2933PubMedSee all References). Of course, this may reflect limited detection of localized [Ca2+]i elevations or an inability to rapidly discharge Ca2+ from the relevant pools (Hardie and Minke 1995xHardie, R.C and Minke, B. Cell Calcium. 1995; 18: 256–274Crossref | PubMed | Scopus (100)See all ReferencesHardie and Minke 1995). Another possibility is that TRP works as a SOC in the direct coupling mode through interactions with the InsP3 receptor (or some other component of the submicrovillar cisternae) to link PLC activation to channel opening. However, either model must address how light absorption in the distal microvillar membrane is communicated to the submicrovillar cisternae and back again over a distance of ∼0.5–1.0 μm with sufficient speed to account for the LIC latency (∼20 ms). Finally, it is possible that TRP is activated directly by one of the many potential signaling compounds generated by PLC.