Bk. Fleischmann et al., VOLTAGE WINDOW FOR SUSTAINED ELEVATION OF CYTOSOLIC CALCIUM IN SMOOTH-MUSCLE CELLS, Proceedings of the National Academy of Sciences of the United Statesof America, 91(25), 1994, pp. 11914-11918
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.