A NOVEL CAPACITATIVE CALCIUM-ENTRY CHANNEL EXPRESSED IN EXCITABLE CELLS

In addition to voltage-gated calcium influx, capacitative calcium entr y (CCE) represents a major pathway for calcium entry into the cell. He re we report the structure, expression and functional properties of a novel CCE channel, TRP5, This channel is a member of a new subfamily o f mammalian homologues of the Drosophila transient receptor potential (TRP) protein, now comprising TRP5 (also CCE2) and the structurally re lated CCE1 (also TRP4), Like TRP4, TRP5 forms ion channels mainly perm eable for Ca2+ which are not active under resting conditions but can b e activated by manoeuvres known to deplete intracellular calcium store s. Accordingly, dialysis of TRPS-expressing cells with inositol-(1,4,5 )-trisphosphate evokes inward rectifying currents which reversed polar ity at potentials more positive than +30 mV, Ca2+ store depletion with thapsigargin induced TRP5-mediated calcium entry dependent on the con centration of extracellular calcium, as seen by dual wavelength fura-2 fluorescence ratio measurements. TRP5 transcripts are expressed almos t exclusively in brain, where they are present in mitral cells of the olfactory bulb, in lateral cerebellar nuclei and, together with TRP4 t ranscripts, in CA1 pyramidal neurons of the hippocampus, indicating th e presence of CCE channels in excitable cells and their participation in neuronal calcium homeostasis.