Effects of extracellular calcium and protons on osteoclast potassium currents

During resorption of mineralized tissues, osteoclasts are exposed to marked changes in the concentration of extracellular Ca2+ and H+. We examined the effects of these cations on two types of K+ currents previously described in these cells. Whole-cell patch clamp recordings of membrane currents were made from osteoclasts freshly isolated from neonatal rats. In control saline (1 mM Ca2+, pH 7.4), the voltage-gated, outwardly rectifying K+ current activates at approximately -45 mV and the conductance is half-maximally activated at -29 mV (V0.5). Increasing [Ca2+]out rapidly and reversibly shifted the current-voltage (I-V) relation to more positive potentials. Current at -29 mV decreased to 28 and 9% of control current at 5 and 10 mM [Ca2+]out, respectively. This effect of elevating [Ca2+]out was due to a positive shift of the K+ channel voltage activation range. Zn2+ or Ni2+ (5 to 500 microM) also shifted the I-V relation to more positive potentials and had additional effects consistent with blockade of the K+ channel. Based on the extent to which these divalent cations affected the voltage activation range of the outwardly rectifying K+ current, the potency sequence was Zn2+ > Ni2+ > Ca2+. Lowering or raising extracellular pH also caused shifts of the voltage activation range to more positive or negative potentials, respectively. In contrast to their effects on the outwardly rectifying K+ current, changes in the concentration of extracellular H+ or Ca2+ did not shift the voltage activation range of the inwardly rectifying K+ current.