CLONING AND FUNCTIONAL EXPRESSION OF A HUMAN CA2-PERMEABLE CATION CHANNEL ACTIVATED BY CALCIUM STORE DEPLETION()

Depletion of intracellular calcium stores generates a signal that acti vates Ca2+-permeable channels in the plasma membrane. We have identifi ed a human cDNA, TRPC1A, from a human fetal brain cDNA library. TRPC1A is homologous to the cation channels trp and trpl in Drosophila and i s a splice variant of the recently identified cDNA Htrp-1. Expression of TRPC1A in CHO cells induced nonselective cation currents with simil ar permeabilities for Na+, Ca2+, and Cs+. The currents were activated by intracellular infusion of myo inositol-1,4,5-trisphosphate or thaps igargin. Expression of TRPC1A significantly enhanced increases in the intracellular free calcium concentration induced by Ca2+ restitution a fter prolonged depletion. Similar results were obtained in Sf9 cells. We conclude that TRPC1A encodes a Ca2+-permeable cation channel activa ted by depletion of intracellular calcium stores.