A Voltage-Dependent Ca2+ Influx Pathway Regulates the Ca2+-Dependent Cl− Conductance of Renal IMCD-3 Cells

A Voltage-Dependent Ca2+ Influx Pathway Regulates the Ca2+-Dependent Cl− Conductance of Renal... We have previously shown that the membrane conductance of mIMCD-3 cells at a holding potential of 0 mV is dominated by a Ca2+-dependent Cl− current (ICLCA). Here we report that ICLCA activity is also voltage dependent and that this dependence on voltage is linked to the opening of a novel Al3+-sensitive, voltage-dependent, Ca2+ influx pathway. Using whole-cell patch-clamp recordings at a physiological holding potential (−60 mV), ICLCA was found to be inactive and resting currents were predominantly K+ selective. However, membrane depolarization to 0 mV resulted in a slow, sigmoidal, activation of ICLCA (T 0.5 ~ 500 s), while repolarization in turn resulted in a monoexponential decay in ICLCA (T 0.5 ~ 100 s). The activation of ICLCA by depolarization was reduced by lowering extracellular Ca2+ and completely inhibited by buffering cytosolic Ca2+ with EGTA, suggesting a role for Ca2+ influx in the activation of ICLCA. However, raising bulk cytosolic Ca2+ at −60 mV did not produce sustained ICLCA activity. Therefore ICLCA is dependent on both an increase in intracellular Ca2+ and depolarization to be active. We further show that membrane depolarization is coupled to opening of a Ca2+ influx pathway that displays equal permeability to Ca2+ and Ba2+ ions and that is blocked by extracellular Al3+ and La3+. Furthermore, Al3+ completely and reversibly inhibited depolarization-induced activation of ICLCA, thereby directly linking Ca2+ influx to activation of ICLCA. We speculate that during sustained membrane depolarization, calcium influx activates ICLCA which functions to modulate NaCl transport across the apical membrane of IMCD cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

A Voltage-Dependent Ca2+ Influx Pathway Regulates the Ca2+-Dependent Cl− Conductance of Renal IMCD-3 Cells

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Copyright © 2009 by Springer Science+Business Media, LLC
Life Sciences; Human Physiology ; Biochemistry, general
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