VOLTAGE WINDOW FOR SUSTAINED ELEVATION OF CYTOSOLIC CALCIUM IN SMOOTH-MUSCLE CELLS

Action potentials activate voltage-dependent calcium channels and atte ndant increases in cytosolic calcium concentration ([Ca2+](i)) in many excitable cells, The role of these channels in the regulation of [Ca2 +](i) in nonspiking cells that do hot depolarize to membrane potential s sufficient to activate a substantial fraction of the available curre nt is less clear, Measurements of the peak activation and steady-state inactivation of L-type calcium currents have predicted the existence of a noninactivating current window over a voltage range where channel inactivation is incomplete. The degree to which such small currents m ight regulate [Ca2+](i), however, has not been established. Here we de monstrate a ''calcium window'' in nondialyzed, quiescent smooth muscle cells over a small voltage range near the resting membrane potential, Sustained depolarizations in this voltage range, but not to more posi tive potentials, resulted in sustained rises in calcium, despite the f act that macroscopic inward currents were <2 pA, The calcium window co rresponded well with the predicted window current determined under the same conditions; the peak of the calcium window occurred at -30 mV, w ith steady-state rises in [Ca2+](i) in some cells at -50 mV, Steady-st ate rises in [Ca2+](i) following depolarization were completely blocke d by nisoldipine and were augmented and shifted to more negative poten tials by BAY K8644. Voltage-dependent calcium channels thus regulate s teady-state calcium levels in nonspiking cells over a voltage range wh ere macroscopic currents are only barely detectable. This voltage rang e is bounded at negative potentials by calcium channel activation and at more positive potentials by channel inactivation.