Permeation through store-operated CRAC channels in divalent-free solution: potential problems and implications for putative CRAC channel genes.

摘要: CRAC channels are key calcium conduits in both physiological and pathological states. Understanding how these controlled is important as this will not only provide insight into a novel signal transduction pathway coupling intracellular stores to the plasma membrane, but might also be of clinical relevance. Determining molecular identity certainly major step forward. Like all Ca(2+)-selective channels, lose their selectivity divalent-free external solution support large monovalent Na(+) currents. This approach has provided new channel permeation selectivity, identifies some interesting differences between voltage-operated (VOCCs). Studies double-edged sword, however. Electrophysiologists need wary because conditions used study I(CRAC) solution, notably omission Mg(2+)/Mg-ATP from recording pipette activates an additional current permeating through Mg(2+)-nucleotide-regulated metal ion (MagNuM; TRPM7) channels. underlies single-channel events that have been attributed past which tool identify store-operated native cells recombinant expression systems.Are we any closer identifying elusive gene(s)? TRPV6 seemed very attractive candidate, one main arguments supporting it was conductance similar for reported under where MagNuM active. We now know approximately 200-fold larger than tissue. Moreover, unclear if store-operated. Further work on TRPV6, particularly whether its still high apparently forms multimers with endogenous activated by variety store depletion protocols, helpful finally resolving issue.