The epithelial calcium channel, ECaC, is activated by hyperpolarization and regulated by cytosolic calcium

The recently cloned epithelial Ca2+ channel, ECaC, which is expressed in th e apical membrane of 1,25-dihydroxyvitamin D-3-responsible epithelia, was c haracterized in Xenopus laevis oocytes by measuring the Ca2+-activated Cl- current which is a sensitive readout of the Ca2+ influx. ECaC-expressing oo cytes responded to a voltage ramp with a maximal inward current of -2.1 +/- 0.3 mu A at a holding potential of -99 +/- 1 mV. The inward current decrea sed progressively at less negative potentials and at +50 mV a small Ca2+-in duced outward current was observed. The Ca2+ influx-evoked current at a hyp erpolarizing pulse to -100 mV displayed a fast activation followed by a rap id but partial inactivation. Loading of the oocytes with the Ca2+ chelator BAPTA delayed the activation and blocked the inactivation of ECaC. When a s eries of brief hyperpolarizing pulses were given a significant decline in t he peak response and subsequent plateau phase was observed. In conclusion, the distinct electrophysiological features of ECaC are hyperpolarization-de pendent activation, Ca2+-dependent regulation of channel conductance and de sensitization during repetitive stimulation. (C) 1999 Academic Press.